Roxanne Nelson, RN, BSN

Incidence rates for testicular cancer have been rising in the United States, as have related mortality rates, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.

Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.

The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.

“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”

She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.

“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”

“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
 

Details of the new findings

For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).

During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).

“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.

They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).

The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.

Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.

However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.

“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”

Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Incidence rates for testicular cancer have been rising in the United States, as have related mortality rates, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.

Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.

The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.

“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”

She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.

“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”

“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
 

Details of the new findings

For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).

During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).

“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.

They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).

The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.

Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.

However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.

“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”

Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Incidence rates for testicular cancer have been rising in the United States, as have related mortality rates, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.

Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.

The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.

“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”

She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.

“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”

“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
 

Details of the new findings

For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).

During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).

“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.

They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).

The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.

Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.

However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.

“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”

Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Oncology Care Model (OCM), launched by the Centers for Medicare & Medicaid Services (CMS) with the goal of reducing spending for Medicare beneficiaries, was “associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes,” according to new findings.

The OCM led to a statistically significant reduction in the use of denosumab – a pricier bone-modifying drug – by patients with bone metastases without changing the overall use of bone-modifying medications. The OCM also prompted more rapid adoption of a less expensive white blood cell growth factor agent – the biosimilar filgrastim – and more selective use of costly antiemetics as primary prophylaxis for chemotherapy-induced nausea.

Overall, the “OCM led to the reduced use of some high-cost supportive care medications, suggesting more value-conscious care,” study author Gabriel A. Brooks, MD, MPH, of the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, N.H., and colleagues write.

The study was published online Feb. 25 in the Journal of Clinical Oncology.

Since the OCM was launched in 2016, several studies have evaluated whether the alternative payment model reached its goal of reducing spending while improving or maintaining the quality of cancer care.

The results have been decidedly mixed.

As previously reported by this news organization, one study found that after 4 years, the OCM led to a $155 million net loss to Medicare. During that time, physician participation in the program also declined, with the number of practices dropping almost 30% between 2016 and 2020.

Other studies, however, have highlighted more positive results.

One large community practice reported saving Medicare $3 million over the course of 1 year. Another analysis found that among community practices that adopted the OCM, in the first year of the program, there was less physician-administered drug use by patients with prostate cancer, lower drug costs by patients with lung and prostate cancer, fewer visits by patients with breast or colon cancer, and lower office-based costs in all cancers analyzed. However, these savings were largely offset by the costs of these programs.

In the current study, DR. Brooks and colleagues compared the use of supportive care medications – bone-modifying drugs as well as prophylactic white blood cell (WBC) growth factors and antiemetics – in practices that adopted the OCM and those that didn’t.

More specifically, the authors zeroed in on the bone-modifying agent denosumab for patients with breast, lung, or prostate cancer and the WBC growth factor biosimilar filgrastim for those receiving chemotherapy for breast, lung, or colorectal cancer. Prophylactic use of higher-cost neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for patients receiving chemotherapy for any type of cancer was also evaluated.

The authors evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims from 2013-2019.

There was a total of 255,638 treatment episodes for bone metastases. The authors found that the OCM led to relative reductions in the use of denosumab but not in the overall use of bone-modifying medications, which included the less costly options zoledronic acid and pamidronate. The use of denosumab was similar for OCM and comparison practices during the baseline period, but during the intervention period, there were statistically significant relative reductions in the use of denosumab at OCM practices for breast (-5.0%), prostate (-4.0%), and lung cancer (-4.1%).

For WBC growth factors, 164,310 episodes were included in analyses. The OCM did not affect the use of prophylactic WBC growth factors during breast cancer chemotherapy for those at high risk of febrile neutropenia but did lead to a relative decrease during intermediate-risk chemotherapy (-7.6%). The authors observed no OCM impact on the use of prophylactic WBC growth factors among intermediate-risk lung or colorectal cancer patients. But, during the intervention period, OCM practices did demonstrate an increased use of originator or biosimilar filgrastim (57.3%) compared to other practices (47.6%), and the quarterly rate of increase in the use of the biosimilar grew 2.6 percentage points faster in OCM practices.

The authors report that there were 414,792 treatment episodes involving the use of prophylactic antiemetics. Overall, among patients receiving chemotherapy with high or moderate emetic risk, the OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists. The authors report a 6.0 percentage point reduction in the use of NK1 antagonists during high-emetic-risk chemotherapy.

“We found that OCM was associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes consistent with value-based care redesign,” the authors conclude. “These impacts on supportive care medication use align with previously reported spending reductions attributable to OCM and suggest that alternative payment models have potential to drive value-based changes in supportive care during cancer treatment.”

The study was supported by CMS. Several of the coauthors have reported relationships with industry, as noted in the article.

A version of this article first appeared on Medscape.com.

The Oncology Care Model (OCM), launched by the Centers for Medicare & Medicaid Services (CMS) with the goal of reducing spending for Medicare beneficiaries, was “associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes,” according to new findings.

The OCM led to a statistically significant reduction in the use of denosumab – a pricier bone-modifying drug – by patients with bone metastases without changing the overall use of bone-modifying medications. The OCM also prompted more rapid adoption of a less expensive white blood cell growth factor agent – the biosimilar filgrastim – and more selective use of costly antiemetics as primary prophylaxis for chemotherapy-induced nausea.

Overall, the “OCM led to the reduced use of some high-cost supportive care medications, suggesting more value-conscious care,” study author Gabriel A. Brooks, MD, MPH, of the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, N.H., and colleagues write.

The study was published online Feb. 25 in the Journal of Clinical Oncology.

Since the OCM was launched in 2016, several studies have evaluated whether the alternative payment model reached its goal of reducing spending while improving or maintaining the quality of cancer care.

The results have been decidedly mixed.

As previously reported by this news organization, one study found that after 4 years, the OCM led to a $155 million net loss to Medicare. During that time, physician participation in the program also declined, with the number of practices dropping almost 30% between 2016 and 2020.

Other studies, however, have highlighted more positive results.

One large community practice reported saving Medicare $3 million over the course of 1 year. Another analysis found that among community practices that adopted the OCM, in the first year of the program, there was less physician-administered drug use by patients with prostate cancer, lower drug costs by patients with lung and prostate cancer, fewer visits by patients with breast or colon cancer, and lower office-based costs in all cancers analyzed. However, these savings were largely offset by the costs of these programs.

In the current study, DR. Brooks and colleagues compared the use of supportive care medications – bone-modifying drugs as well as prophylactic white blood cell (WBC) growth factors and antiemetics – in practices that adopted the OCM and those that didn’t.

More specifically, the authors zeroed in on the bone-modifying agent denosumab for patients with breast, lung, or prostate cancer and the WBC growth factor biosimilar filgrastim for those receiving chemotherapy for breast, lung, or colorectal cancer. Prophylactic use of higher-cost neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for patients receiving chemotherapy for any type of cancer was also evaluated.

The authors evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims from 2013-2019.

There was a total of 255,638 treatment episodes for bone metastases. The authors found that the OCM led to relative reductions in the use of denosumab but not in the overall use of bone-modifying medications, which included the less costly options zoledronic acid and pamidronate. The use of denosumab was similar for OCM and comparison practices during the baseline period, but during the intervention period, there were statistically significant relative reductions in the use of denosumab at OCM practices for breast (-5.0%), prostate (-4.0%), and lung cancer (-4.1%).

For WBC growth factors, 164,310 episodes were included in analyses. The OCM did not affect the use of prophylactic WBC growth factors during breast cancer chemotherapy for those at high risk of febrile neutropenia but did lead to a relative decrease during intermediate-risk chemotherapy (-7.6%). The authors observed no OCM impact on the use of prophylactic WBC growth factors among intermediate-risk lung or colorectal cancer patients. But, during the intervention period, OCM practices did demonstrate an increased use of originator or biosimilar filgrastim (57.3%) compared to other practices (47.6%), and the quarterly rate of increase in the use of the biosimilar grew 2.6 percentage points faster in OCM practices.

The authors report that there were 414,792 treatment episodes involving the use of prophylactic antiemetics. Overall, among patients receiving chemotherapy with high or moderate emetic risk, the OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists. The authors report a 6.0 percentage point reduction in the use of NK1 antagonists during high-emetic-risk chemotherapy.

“We found that OCM was associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes consistent with value-based care redesign,” the authors conclude. “These impacts on supportive care medication use align with previously reported spending reductions attributable to OCM and suggest that alternative payment models have potential to drive value-based changes in supportive care during cancer treatment.”

The study was supported by CMS. Several of the coauthors have reported relationships with industry, as noted in the article.

A version of this article first appeared on Medscape.com.

The Oncology Care Model (OCM), launched by the Centers for Medicare & Medicaid Services (CMS) with the goal of reducing spending for Medicare beneficiaries, was “associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes,” according to new findings.

The OCM led to a statistically significant reduction in the use of denosumab – a pricier bone-modifying drug – by patients with bone metastases without changing the overall use of bone-modifying medications. The OCM also prompted more rapid adoption of a less expensive white blood cell growth factor agent – the biosimilar filgrastim – and more selective use of costly antiemetics as primary prophylaxis for chemotherapy-induced nausea.

Overall, the “OCM led to the reduced use of some high-cost supportive care medications, suggesting more value-conscious care,” study author Gabriel A. Brooks, MD, MPH, of the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, N.H., and colleagues write.

The study was published online Feb. 25 in the Journal of Clinical Oncology.

Since the OCM was launched in 2016, several studies have evaluated whether the alternative payment model reached its goal of reducing spending while improving or maintaining the quality of cancer care.

The results have been decidedly mixed.

As previously reported by this news organization, one study found that after 4 years, the OCM led to a $155 million net loss to Medicare. During that time, physician participation in the program also declined, with the number of practices dropping almost 30% between 2016 and 2020.

Other studies, however, have highlighted more positive results.

One large community practice reported saving Medicare $3 million over the course of 1 year. Another analysis found that among community practices that adopted the OCM, in the first year of the program, there was less physician-administered drug use by patients with prostate cancer, lower drug costs by patients with lung and prostate cancer, fewer visits by patients with breast or colon cancer, and lower office-based costs in all cancers analyzed. However, these savings were largely offset by the costs of these programs.

In the current study, DR. Brooks and colleagues compared the use of supportive care medications – bone-modifying drugs as well as prophylactic white blood cell (WBC) growth factors and antiemetics – in practices that adopted the OCM and those that didn’t.

More specifically, the authors zeroed in on the bone-modifying agent denosumab for patients with breast, lung, or prostate cancer and the WBC growth factor biosimilar filgrastim for those receiving chemotherapy for breast, lung, or colorectal cancer. Prophylactic use of higher-cost neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for patients receiving chemotherapy for any type of cancer was also evaluated.

The authors evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims from 2013-2019.

There was a total of 255,638 treatment episodes for bone metastases. The authors found that the OCM led to relative reductions in the use of denosumab but not in the overall use of bone-modifying medications, which included the less costly options zoledronic acid and pamidronate. The use of denosumab was similar for OCM and comparison practices during the baseline period, but during the intervention period, there were statistically significant relative reductions in the use of denosumab at OCM practices for breast (-5.0%), prostate (-4.0%), and lung cancer (-4.1%).

For WBC growth factors, 164,310 episodes were included in analyses. The OCM did not affect the use of prophylactic WBC growth factors during breast cancer chemotherapy for those at high risk of febrile neutropenia but did lead to a relative decrease during intermediate-risk chemotherapy (-7.6%). The authors observed no OCM impact on the use of prophylactic WBC growth factors among intermediate-risk lung or colorectal cancer patients. But, during the intervention period, OCM practices did demonstrate an increased use of originator or biosimilar filgrastim (57.3%) compared to other practices (47.6%), and the quarterly rate of increase in the use of the biosimilar grew 2.6 percentage points faster in OCM practices.

The authors report that there were 414,792 treatment episodes involving the use of prophylactic antiemetics. Overall, among patients receiving chemotherapy with high or moderate emetic risk, the OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists. The authors report a 6.0 percentage point reduction in the use of NK1 antagonists during high-emetic-risk chemotherapy.

“We found that OCM was associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes consistent with value-based care redesign,” the authors conclude. “These impacts on supportive care medication use align with previously reported spending reductions attributable to OCM and suggest that alternative payment models have potential to drive value-based changes in supportive care during cancer treatment.”

The study was supported by CMS. Several of the coauthors have reported relationships with industry, as noted in the article.

A version of this article first appeared on Medscape.com.

Among patients with ovarian cancer who have achieved remission, routine surveillance with virtual appointments, along with tumor marker monitoring and imaging, may offer an alternative to the currently mandated frequent in-person visits.

The suggestion comes from Jacqueline Feinberg, MD, gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, and colleagues, who conducted a retrospective study of 147 patients who experienced ovarian cancer recurrence within 2 years of their first clinical remission, and found that none of these recurrences were detected by physical examination alone.

About one third of these patients had a recurrence that was first detected by tumor marker, over half by imaging, and the rest by the presentation of new symptoms and biopsies taken during nononcologic surgery.

“This finding suggests that virtual visits, which have quickly gained acceptance during the COVID-19 pandemic, combined with a surveillance protocol for tumor marker testing and imaging, may be sufficient to identify ovarian cancer recurrence,” the team concluded. The study was published in the International Journal of Gynecologic Cancer.

The COVID-19 pandemic has accelerated the use of telemedicine, with new international guidelines recommending minimizing in-person contact, noted the authors.

They wondered how this would work in patients who have achieved remission from ovarian cancer.

At MSKCC, the usual surveillance protocol for the first 2 years after ovarian cancer remission includes an in-person physical examination every 3 months, along with CA-125 testing and imaging of the chest, abdomen, and pelvis. For year 3, the time between surveillance testing is extended to every 3-6 months, for the fourth and fifth year, to every 6 months. Beyond 5 years, physical examination and testing for the protein CA-125 are performed annually, and imaging is optional.

However, there is no strong evidence to support this current surveillance regimen, the authors pointed out. They sought to determine if it was possible to do virtual visits instead, along with tumor marker monitoring and imaging.
 

Evidence for virtual exams

To answer that question, Dr. Feinberg and colleagues conducted a retrospective study that included patients who were initially seen from January 2015 to December 2017, and who had achieved clinical remission and then experienced ovarian cancer recurrence with 2 years of remission.

A total of 147 patients were included in the final analysis. None of these patients had their recurrence detected on routine physical exam, including pelvic exam, as the primary method of detection. More than half of patients (n = 81; 55%) had their recurrence detected on radiographic scan, whereas for 46 patients (31%), it was by tumor marker. Among the remaining patients, 17 (12%) experienced new symptoms and for 3 (2%), it was by biopsy during a nononcologic surgery.

By the time treatment was initiated for recurrence, 111 patients (75%) had multiple positive findings; 48 (33%) had symptoms, 21 (14%) had physical exam findings, 106 (72%) had increases in their tumor markers, and 141 (96%) had changes on their imaging.

In addition, 131 (89%) had baseline increases in CA-125, and of 16 remaining patients, 12 experienced a CA-125 increase during recurrence.

There were 21 patients who had positive physical exam findings following their recurrence, which had already been detected. Within this subset, 19 had concurrent symptoms, and for 6 of them, symptom onset had been the primary method of detection. For the 2 patients without symptoms, recurrence was initially detected by a rise in CA-125 on routine check in one patient, by surveillance imaging in the other.

The authors are now planning a pilot virtual intensive surveillance program, where they will evaluate patient-reported outcomes

The study was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. Study author Dennis Chi, MD, reports personal fees from Bovie Medical (now Apyx Medical), Verthermia, C Surgeries, and Biom’Up, and is also a former stockholder of Intuitive Surgical and TransEnterix. The other authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among patients with ovarian cancer who have achieved remission, routine surveillance with virtual appointments, along with tumor marker monitoring and imaging, may offer an alternative to the currently mandated frequent in-person visits.

The suggestion comes from Jacqueline Feinberg, MD, gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, and colleagues, who conducted a retrospective study of 147 patients who experienced ovarian cancer recurrence within 2 years of their first clinical remission, and found that none of these recurrences were detected by physical examination alone.

About one third of these patients had a recurrence that was first detected by tumor marker, over half by imaging, and the rest by the presentation of new symptoms and biopsies taken during nononcologic surgery.

“This finding suggests that virtual visits, which have quickly gained acceptance during the COVID-19 pandemic, combined with a surveillance protocol for tumor marker testing and imaging, may be sufficient to identify ovarian cancer recurrence,” the team concluded. The study was published in the International Journal of Gynecologic Cancer.

The COVID-19 pandemic has accelerated the use of telemedicine, with new international guidelines recommending minimizing in-person contact, noted the authors.

They wondered how this would work in patients who have achieved remission from ovarian cancer.

At MSKCC, the usual surveillance protocol for the first 2 years after ovarian cancer remission includes an in-person physical examination every 3 months, along with CA-125 testing and imaging of the chest, abdomen, and pelvis. For year 3, the time between surveillance testing is extended to every 3-6 months, for the fourth and fifth year, to every 6 months. Beyond 5 years, physical examination and testing for the protein CA-125 are performed annually, and imaging is optional.

However, there is no strong evidence to support this current surveillance regimen, the authors pointed out. They sought to determine if it was possible to do virtual visits instead, along with tumor marker monitoring and imaging.
 

Evidence for virtual exams

To answer that question, Dr. Feinberg and colleagues conducted a retrospective study that included patients who were initially seen from January 2015 to December 2017, and who had achieved clinical remission and then experienced ovarian cancer recurrence with 2 years of remission.

A total of 147 patients were included in the final analysis. None of these patients had their recurrence detected on routine physical exam, including pelvic exam, as the primary method of detection. More than half of patients (n = 81; 55%) had their recurrence detected on radiographic scan, whereas for 46 patients (31%), it was by tumor marker. Among the remaining patients, 17 (12%) experienced new symptoms and for 3 (2%), it was by biopsy during a nononcologic surgery.

By the time treatment was initiated for recurrence, 111 patients (75%) had multiple positive findings; 48 (33%) had symptoms, 21 (14%) had physical exam findings, 106 (72%) had increases in their tumor markers, and 141 (96%) had changes on their imaging.

In addition, 131 (89%) had baseline increases in CA-125, and of 16 remaining patients, 12 experienced a CA-125 increase during recurrence.

There were 21 patients who had positive physical exam findings following their recurrence, which had already been detected. Within this subset, 19 had concurrent symptoms, and for 6 of them, symptom onset had been the primary method of detection. For the 2 patients without symptoms, recurrence was initially detected by a rise in CA-125 on routine check in one patient, by surveillance imaging in the other.

The authors are now planning a pilot virtual intensive surveillance program, where they will evaluate patient-reported outcomes

The study was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. Study author Dennis Chi, MD, reports personal fees from Bovie Medical (now Apyx Medical), Verthermia, C Surgeries, and Biom’Up, and is also a former stockholder of Intuitive Surgical and TransEnterix. The other authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among patients with ovarian cancer who have achieved remission, routine surveillance with virtual appointments, along with tumor marker monitoring and imaging, may offer an alternative to the currently mandated frequent in-person visits.

The suggestion comes from Jacqueline Feinberg, MD, gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, and colleagues, who conducted a retrospective study of 147 patients who experienced ovarian cancer recurrence within 2 years of their first clinical remission, and found that none of these recurrences were detected by physical examination alone.

About one third of these patients had a recurrence that was first detected by tumor marker, over half by imaging, and the rest by the presentation of new symptoms and biopsies taken during nononcologic surgery.

“This finding suggests that virtual visits, which have quickly gained acceptance during the COVID-19 pandemic, combined with a surveillance protocol for tumor marker testing and imaging, may be sufficient to identify ovarian cancer recurrence,” the team concluded. The study was published in the International Journal of Gynecologic Cancer.

The COVID-19 pandemic has accelerated the use of telemedicine, with new international guidelines recommending minimizing in-person contact, noted the authors.

They wondered how this would work in patients who have achieved remission from ovarian cancer.

At MSKCC, the usual surveillance protocol for the first 2 years after ovarian cancer remission includes an in-person physical examination every 3 months, along with CA-125 testing and imaging of the chest, abdomen, and pelvis. For year 3, the time between surveillance testing is extended to every 3-6 months, for the fourth and fifth year, to every 6 months. Beyond 5 years, physical examination and testing for the protein CA-125 are performed annually, and imaging is optional.

However, there is no strong evidence to support this current surveillance regimen, the authors pointed out. They sought to determine if it was possible to do virtual visits instead, along with tumor marker monitoring and imaging.
 

Evidence for virtual exams

To answer that question, Dr. Feinberg and colleagues conducted a retrospective study that included patients who were initially seen from January 2015 to December 2017, and who had achieved clinical remission and then experienced ovarian cancer recurrence with 2 years of remission.

A total of 147 patients were included in the final analysis. None of these patients had their recurrence detected on routine physical exam, including pelvic exam, as the primary method of detection. More than half of patients (n = 81; 55%) had their recurrence detected on radiographic scan, whereas for 46 patients (31%), it was by tumor marker. Among the remaining patients, 17 (12%) experienced new symptoms and for 3 (2%), it was by biopsy during a nononcologic surgery.

By the time treatment was initiated for recurrence, 111 patients (75%) had multiple positive findings; 48 (33%) had symptoms, 21 (14%) had physical exam findings, 106 (72%) had increases in their tumor markers, and 141 (96%) had changes on their imaging.

In addition, 131 (89%) had baseline increases in CA-125, and of 16 remaining patients, 12 experienced a CA-125 increase during recurrence.

There were 21 patients who had positive physical exam findings following their recurrence, which had already been detected. Within this subset, 19 had concurrent symptoms, and for 6 of them, symptom onset had been the primary method of detection. For the 2 patients without symptoms, recurrence was initially detected by a rise in CA-125 on routine check in one patient, by surveillance imaging in the other.

The authors are now planning a pilot virtual intensive surveillance program, where they will evaluate patient-reported outcomes

The study was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. Study author Dennis Chi, MD, reports personal fees from Bovie Medical (now Apyx Medical), Verthermia, C Surgeries, and Biom’Up, and is also a former stockholder of Intuitive Surgical and TransEnterix. The other authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO — A blood test that measures circulating tumor DNA (ctDNA) can help to identify those patients with resectable colorectal cancer who are most likely to derive the most benefit from adjuvant chemotherapy, suggest results from a Japanese study.

The team used a personalized tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay) to measure molecular residual disease (MRD) 4 weeks after surgery.

Among patients who were ctDNA positive at 4 weeks post-op, those who received adjuvant chemotherapy had significantly longer disease-free survival (DFS) at 6 months, compared with patients who didn’t receive it.

The adjuvant chemotherapy was able to clear ctDNA in 68% of that subgroup by 24 weeks, noted study author Masahito Kotaka, MD, PhD, from the gastrointestinal cancer center, Sano Hospital, Hyogo, Japan

“Even with an extended follow-up time, ctDNA positivity at 4 weeks post-op was significantly associated with inferior disease-free survival,” he said.

“Two out of three post-op patients who were positive at 4 weeks recurred, even in stage I or low-risk stage II.”

However, he noted that “patients who were 4 weeks post-op and ctDNA negative did not derive significant benefit from adjuvant chemotherapy in high- risk stage II and III.”

Overall, the study shows that stratifying postsurgical treatment decisions using the assay can identify patients likely to benefit from adjuvant chemotherapy across all stages of the disease, explained Dr. Kotaka.

Dr. Kotaka presented the new results at the Gastrointestinal Cancers Symposium.

“ctDNA dynamics from 4-week post-op positivity to 12 weeks afterwards could become new surrogate endpoints beyond disease-free survival,” he suggested.

However, the discussant for this abstract, Rona Yaeger, MD, from Memorial Sloan Kettering Cancer Center in New York, cautioned that this is not yet ready for clinical use.

“There was a clear prognostic effect,” she said. “This was a very large sample size and validates some of the earlier studies showing that ctDNA is a very important prognostic marker.” This study “gives us a tighter confidence interval due to the large size.”

However, there are limitations, one being that it was not a randomized study so it is unknown who received adjuvant therapy, she pointed out. “Since it is not randomized, the groups are not equal.”

Summarizing, she said that ctDNA is a strong prognostic marker that identifies MRD. “But it is expensive and currently doesn’t guide our adjuvant decisions,” she said. “It is not ready yet for standard evaluation of early-stage colorectal cancer patients, and we don’t know yet if additional therapy after adjuvant therapy in ctDNA-positive patients will change outcomes.”
 

Study details

The new results come from the GALAXY study, which is part of a large platform in Japan, called CIRCULATE, that is evaluating the clinical utility of ctDNA in patients with resectable colorectal cancer. Aside from GALAXY, which is a prospective observational trial, CIRCULATE also includes two phase 3 randomized trials: VEGA and ALTAIR.

For their study, Dr. Kotaka and colleagues monitored ctDNA status in patients with clinical stage l to IV colorectal cancer who underwent complete surgical resection and then evaluated the association of ctDNA dynamics with a short-term clinical outcome and adjuvant therapy efficacy.

A total of 1,040 patients were included in the current analysis. They were stratified into subgroups that were either ctDNA positive (n = 183) or ctDNA negative (n = 531) 4 weeks post surgery. The cohort included 116 patients with stage I disease, 478 with stage II, 503 with stage III, and 268 patients with oligomet resectable stage IV (of whom 16% received neoadjuvant chemotherapy).

Blood samples were collected before surgery and at 4, 12, 24, 36, 48, 72, and 96 weeks following resection.

The team looked at 6-month disease-free survival rates. Among patients with high-risk stage II disease and with a positive ctDNA assay at 4 weeks post-op, those who received adjuvant chemotherapy had a 6-month DFS rate of 100% vs. 53.8% who did not receive adjuvant chemotherapy.

For stage III disease, those rates were 89.2% vs. 32.0%, and for stage IV disease, they were 72.7% vs. 28.3%.

At a median follow-up of 11.4 months, the 6- and 12-month DFS was 96.5% and 92.7% for all patients who were ctDNA negative at 4 weeks post-op. Outcomes for patients who were ctDNA positive were significantly poorer, at 62.8% and 47.5% (hazard ratio, 10.9; P <.001; sensitivity for recurrence, 63.6%).

Of the 188 patients who were MRD positive at 4 weeks post-op with available MRD status at 12 weeks, 95 received adjuvant therapy. The ctDNA clearance rate at 12 weeks was significantly higher in the adjuvant therapy group vs. no adjuvant therapy; 57% vs. 8% in stage I-IV (P < .001), and 58% vs. 11% (4/37) in stage II–III (P < .001).

Additionally, the ctDNA clearance rate at 24 weeks was also significantly higher in adjuvant vs. no adjuvant therapy arms; 26% vs. 0% in patients with stage I-IV disease (P = .003), and 33% vs. 0% in patients with stage II-III disease (P = .03).

Cumulative clearance of ctDNA at 6 months post-op was significantly higher in the adjuvant vs. no adjuvant therapy arms (67% vs. 7% by 24 weeks; cumulative HR, 17.1; P < .001). For patients MRD positive at 4 weeks, the 6-month DFS was also significantly higher in adjuvant vs. no adjuvant therapy arms; 84% vs 34% (HR, 0.15; P < .001), which was observed across all stages.

Upon multivariate analysis, the highest risk of recurrence for patients with stage II-III cancer correlated with ctDNA-positive vs. ctDNA-negative status (HR, 15.3; P <. 001), mutant vs. wild-type RAS (HR, 1.8; P = .04), or mutant vs. wild-type BRAF (HR, 5.2; P < .001).

The group is continuing with its research into a ctDNA-guided adjuvant strategy. More data will be available soon from the ongoing randomized VEGA and ALTAIR studies and will be presented at future conference, Dr. Kotaka commented.

CIRCULATE‐Japan receives financial supports from the Japan Agency for Medical Research and Development and from Taiho Pharmaceutical, through Alpha‐A. Dr. Kotaka reported relationships with Chugai, Lilly Japan, Taiho, Takeda, and Yakult Honsha. Dr. Yaeger reported relationships with Array BioPharma, Boehringer Ingelheim, Mirati Therapeutics, Natera, and Pfizer.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO — A blood test that measures circulating tumor DNA (ctDNA) can help to identify those patients with resectable colorectal cancer who are most likely to derive the most benefit from adjuvant chemotherapy, suggest results from a Japanese study.

The team used a personalized tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay) to measure molecular residual disease (MRD) 4 weeks after surgery.

Among patients who were ctDNA positive at 4 weeks post-op, those who received adjuvant chemotherapy had significantly longer disease-free survival (DFS) at 6 months, compared with patients who didn’t receive it.

The adjuvant chemotherapy was able to clear ctDNA in 68% of that subgroup by 24 weeks, noted study author Masahito Kotaka, MD, PhD, from the gastrointestinal cancer center, Sano Hospital, Hyogo, Japan

“Even with an extended follow-up time, ctDNA positivity at 4 weeks post-op was significantly associated with inferior disease-free survival,” he said.

“Two out of three post-op patients who were positive at 4 weeks recurred, even in stage I or low-risk stage II.”

However, he noted that “patients who were 4 weeks post-op and ctDNA negative did not derive significant benefit from adjuvant chemotherapy in high- risk stage II and III.”

Overall, the study shows that stratifying postsurgical treatment decisions using the assay can identify patients likely to benefit from adjuvant chemotherapy across all stages of the disease, explained Dr. Kotaka.

Dr. Kotaka presented the new results at the Gastrointestinal Cancers Symposium.

“ctDNA dynamics from 4-week post-op positivity to 12 weeks afterwards could become new surrogate endpoints beyond disease-free survival,” he suggested.

However, the discussant for this abstract, Rona Yaeger, MD, from Memorial Sloan Kettering Cancer Center in New York, cautioned that this is not yet ready for clinical use.

“There was a clear prognostic effect,” she said. “This was a very large sample size and validates some of the earlier studies showing that ctDNA is a very important prognostic marker.” This study “gives us a tighter confidence interval due to the large size.”

However, there are limitations, one being that it was not a randomized study so it is unknown who received adjuvant therapy, she pointed out. “Since it is not randomized, the groups are not equal.”

Summarizing, she said that ctDNA is a strong prognostic marker that identifies MRD. “But it is expensive and currently doesn’t guide our adjuvant decisions,” she said. “It is not ready yet for standard evaluation of early-stage colorectal cancer patients, and we don’t know yet if additional therapy after adjuvant therapy in ctDNA-positive patients will change outcomes.”
 

Study details

The new results come from the GALAXY study, which is part of a large platform in Japan, called CIRCULATE, that is evaluating the clinical utility of ctDNA in patients with resectable colorectal cancer. Aside from GALAXY, which is a prospective observational trial, CIRCULATE also includes two phase 3 randomized trials: VEGA and ALTAIR.

For their study, Dr. Kotaka and colleagues monitored ctDNA status in patients with clinical stage l to IV colorectal cancer who underwent complete surgical resection and then evaluated the association of ctDNA dynamics with a short-term clinical outcome and adjuvant therapy efficacy.

A total of 1,040 patients were included in the current analysis. They were stratified into subgroups that were either ctDNA positive (n = 183) or ctDNA negative (n = 531) 4 weeks post surgery. The cohort included 116 patients with stage I disease, 478 with stage II, 503 with stage III, and 268 patients with oligomet resectable stage IV (of whom 16% received neoadjuvant chemotherapy).

Blood samples were collected before surgery and at 4, 12, 24, 36, 48, 72, and 96 weeks following resection.

The team looked at 6-month disease-free survival rates. Among patients with high-risk stage II disease and with a positive ctDNA assay at 4 weeks post-op, those who received adjuvant chemotherapy had a 6-month DFS rate of 100% vs. 53.8% who did not receive adjuvant chemotherapy.

For stage III disease, those rates were 89.2% vs. 32.0%, and for stage IV disease, they were 72.7% vs. 28.3%.

At a median follow-up of 11.4 months, the 6- and 12-month DFS was 96.5% and 92.7% for all patients who were ctDNA negative at 4 weeks post-op. Outcomes for patients who were ctDNA positive were significantly poorer, at 62.8% and 47.5% (hazard ratio, 10.9; P <.001; sensitivity for recurrence, 63.6%).

Of the 188 patients who were MRD positive at 4 weeks post-op with available MRD status at 12 weeks, 95 received adjuvant therapy. The ctDNA clearance rate at 12 weeks was significantly higher in the adjuvant therapy group vs. no adjuvant therapy; 57% vs. 8% in stage I-IV (P < .001), and 58% vs. 11% (4/37) in stage II–III (P < .001).

Additionally, the ctDNA clearance rate at 24 weeks was also significantly higher in adjuvant vs. no adjuvant therapy arms; 26% vs. 0% in patients with stage I-IV disease (P = .003), and 33% vs. 0% in patients with stage II-III disease (P = .03).

Cumulative clearance of ctDNA at 6 months post-op was significantly higher in the adjuvant vs. no adjuvant therapy arms (67% vs. 7% by 24 weeks; cumulative HR, 17.1; P < .001). For patients MRD positive at 4 weeks, the 6-month DFS was also significantly higher in adjuvant vs. no adjuvant therapy arms; 84% vs 34% (HR, 0.15; P < .001), which was observed across all stages.

Upon multivariate analysis, the highest risk of recurrence for patients with stage II-III cancer correlated with ctDNA-positive vs. ctDNA-negative status (HR, 15.3; P <. 001), mutant vs. wild-type RAS (HR, 1.8; P = .04), or mutant vs. wild-type BRAF (HR, 5.2; P < .001).

The group is continuing with its research into a ctDNA-guided adjuvant strategy. More data will be available soon from the ongoing randomized VEGA and ALTAIR studies and will be presented at future conference, Dr. Kotaka commented.

CIRCULATE‐Japan receives financial supports from the Japan Agency for Medical Research and Development and from Taiho Pharmaceutical, through Alpha‐A. Dr. Kotaka reported relationships with Chugai, Lilly Japan, Taiho, Takeda, and Yakult Honsha. Dr. Yaeger reported relationships with Array BioPharma, Boehringer Ingelheim, Mirati Therapeutics, Natera, and Pfizer.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO — A blood test that measures circulating tumor DNA (ctDNA) can help to identify those patients with resectable colorectal cancer who are most likely to derive the most benefit from adjuvant chemotherapy, suggest results from a Japanese study.

The team used a personalized tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay) to measure molecular residual disease (MRD) 4 weeks after surgery.

Among patients who were ctDNA positive at 4 weeks post-op, those who received adjuvant chemotherapy had significantly longer disease-free survival (DFS) at 6 months, compared with patients who didn’t receive it.

The adjuvant chemotherapy was able to clear ctDNA in 68% of that subgroup by 24 weeks, noted study author Masahito Kotaka, MD, PhD, from the gastrointestinal cancer center, Sano Hospital, Hyogo, Japan

“Even with an extended follow-up time, ctDNA positivity at 4 weeks post-op was significantly associated with inferior disease-free survival,” he said.

“Two out of three post-op patients who were positive at 4 weeks recurred, even in stage I or low-risk stage II.”

However, he noted that “patients who were 4 weeks post-op and ctDNA negative did not derive significant benefit from adjuvant chemotherapy in high- risk stage II and III.”

Overall, the study shows that stratifying postsurgical treatment decisions using the assay can identify patients likely to benefit from adjuvant chemotherapy across all stages of the disease, explained Dr. Kotaka.

Dr. Kotaka presented the new results at the Gastrointestinal Cancers Symposium.

“ctDNA dynamics from 4-week post-op positivity to 12 weeks afterwards could become new surrogate endpoints beyond disease-free survival,” he suggested.

However, the discussant for this abstract, Rona Yaeger, MD, from Memorial Sloan Kettering Cancer Center in New York, cautioned that this is not yet ready for clinical use.

“There was a clear prognostic effect,” she said. “This was a very large sample size and validates some of the earlier studies showing that ctDNA is a very important prognostic marker.” This study “gives us a tighter confidence interval due to the large size.”

However, there are limitations, one being that it was not a randomized study so it is unknown who received adjuvant therapy, she pointed out. “Since it is not randomized, the groups are not equal.”

Summarizing, she said that ctDNA is a strong prognostic marker that identifies MRD. “But it is expensive and currently doesn’t guide our adjuvant decisions,” she said. “It is not ready yet for standard evaluation of early-stage colorectal cancer patients, and we don’t know yet if additional therapy after adjuvant therapy in ctDNA-positive patients will change outcomes.”
 

Study details

The new results come from the GALAXY study, which is part of a large platform in Japan, called CIRCULATE, that is evaluating the clinical utility of ctDNA in patients with resectable colorectal cancer. Aside from GALAXY, which is a prospective observational trial, CIRCULATE also includes two phase 3 randomized trials: VEGA and ALTAIR.

For their study, Dr. Kotaka and colleagues monitored ctDNA status in patients with clinical stage l to IV colorectal cancer who underwent complete surgical resection and then evaluated the association of ctDNA dynamics with a short-term clinical outcome and adjuvant therapy efficacy.

A total of 1,040 patients were included in the current analysis. They were stratified into subgroups that were either ctDNA positive (n = 183) or ctDNA negative (n = 531) 4 weeks post surgery. The cohort included 116 patients with stage I disease, 478 with stage II, 503 with stage III, and 268 patients with oligomet resectable stage IV (of whom 16% received neoadjuvant chemotherapy).

Blood samples were collected before surgery and at 4, 12, 24, 36, 48, 72, and 96 weeks following resection.

The team looked at 6-month disease-free survival rates. Among patients with high-risk stage II disease and with a positive ctDNA assay at 4 weeks post-op, those who received adjuvant chemotherapy had a 6-month DFS rate of 100% vs. 53.8% who did not receive adjuvant chemotherapy.

For stage III disease, those rates were 89.2% vs. 32.0%, and for stage IV disease, they were 72.7% vs. 28.3%.

At a median follow-up of 11.4 months, the 6- and 12-month DFS was 96.5% and 92.7% for all patients who were ctDNA negative at 4 weeks post-op. Outcomes for patients who were ctDNA positive were significantly poorer, at 62.8% and 47.5% (hazard ratio, 10.9; P <.001; sensitivity for recurrence, 63.6%).

Of the 188 patients who were MRD positive at 4 weeks post-op with available MRD status at 12 weeks, 95 received adjuvant therapy. The ctDNA clearance rate at 12 weeks was significantly higher in the adjuvant therapy group vs. no adjuvant therapy; 57% vs. 8% in stage I-IV (P < .001), and 58% vs. 11% (4/37) in stage II–III (P < .001).

Additionally, the ctDNA clearance rate at 24 weeks was also significantly higher in adjuvant vs. no adjuvant therapy arms; 26% vs. 0% in patients with stage I-IV disease (P = .003), and 33% vs. 0% in patients with stage II-III disease (P = .03).

Cumulative clearance of ctDNA at 6 months post-op was significantly higher in the adjuvant vs. no adjuvant therapy arms (67% vs. 7% by 24 weeks; cumulative HR, 17.1; P < .001). For patients MRD positive at 4 weeks, the 6-month DFS was also significantly higher in adjuvant vs. no adjuvant therapy arms; 84% vs 34% (HR, 0.15; P < .001), which was observed across all stages.

Upon multivariate analysis, the highest risk of recurrence for patients with stage II-III cancer correlated with ctDNA-positive vs. ctDNA-negative status (HR, 15.3; P <. 001), mutant vs. wild-type RAS (HR, 1.8; P = .04), or mutant vs. wild-type BRAF (HR, 5.2; P < .001).

The group is continuing with its research into a ctDNA-guided adjuvant strategy. More data will be available soon from the ongoing randomized VEGA and ALTAIR studies and will be presented at future conference, Dr. Kotaka commented.

CIRCULATE‐Japan receives financial supports from the Japan Agency for Medical Research and Development and from Taiho Pharmaceutical, through Alpha‐A. Dr. Kotaka reported relationships with Chugai, Lilly Japan, Taiho, Takeda, and Yakult Honsha. Dr. Yaeger reported relationships with Array BioPharma, Boehringer Ingelheim, Mirati Therapeutics, Natera, and Pfizer.

A version of this article first appeared on Medscape.com.

A novel dual immunotherapy regimen significantly improved overall survival compared to a standard of care in patients with advanced, unresectable hepatocellular carcinoma (HCC) in the large phase 3 HIMALAYA trial.

The novel regimen, dubbed STRIDE (Single T Regular Interval D), comprised a single priming dose of the investigational agent tremelimumab followed by regular doses of durvalumab (Imfinzi).

Patients on this regimen experienced a 22% lower risk of death than patients treated with sorafenib (Nexavar), which at the time the trial began was the only approved frontline standard of care for patients with advanced HCC.

At 3 years, almost 31% of patients treated with combination therapy were still alive, versus 24.7% for durvalumab alone and 20.2% for sorafenib.

This novel regimen “may represent new treatment options for patients with untreated hepatocellular carcinoma,” said lead author Ghassan Abou-Alfa, MD, MBA, an attending physician at Memorial Sloan Kettering Comprehensive Cancer Center, New York. “Pending FDA approval, this novel dual immunotherapy regimen could be readily available to all patients and would not require additional safety assessments prior to treatment.”

He presented the new results here at the Gastrointestinal Cancers Symposium (GICS) 2022.

Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, agreed that the STRIDE regimen, with the combination of one priming dose of tremelimumab and regular interval durvalumab, is a new first-line treatment option for advanced HCC patients.

“But there are some limitations to the study and topics that will require further additional investigation,” he added.
 

Liver cancer increasing

Liver cancer is one of the few cancers for which deaths rates are increasing. In the United States. The overall rate of death due to liver cancer has doubled since 1980, Dr. Abou-Alfa told the audience. The most recent 5-year survival rates are 32.6% for localized disease, 10.8% with regional disease, and 2.4% with distant disease.

Until recently, first-line treatment for untreated HCC was limited to the multikinase inhibitors sorafenib and lenvatinib (Lenvima), which have been associated with median overall survival of approximately 1 year but also with toxicities that impact the quality of life, he commented.

“More recently, the anti-PD-L1 agent atezolizumab plus bevacizumab showed significant survival benefit versus sorafenib and have become a standard of care following approval in 2020,” Dr. Abou-Alfa said.

Tremelimumab is an experimental immunotherapy that targets the CTLA-4 receptor, and in 2020 it received orphan drug status for the treatment of HCC from the U.S. Food and Drug Administration. The authors hypothesized that tremelimumab would boost the response to durvalumab, a PDL-1 inhibitor, as this had been observed in the phase 2 Study 22 trial, which had tested the STRIDE regimen.

Now in the phase 3 HIMALAYA trial, the STRIDE regimen was compared to durvalumab used alone and to sorafenib used alone.

The trial randomized 1,171 patients to receive either the STRIDE regimen (a single dose of 75 mg tremelimumab plus 1,500 mg durvalumab every 4 weeks) or durvalumab alone (1,500 mg every 4 weeks) or sorafenib alone (400 mg twice daily).

Initially, there was also a lower-dose tremelimumab-containing arm, but recruitment into this arm was halted after a planned analysis of Study 22 failed to show a meaningful efficacy difference between that arm and durvalumab alone.

At data cutoff, the study’s primary objective was met. Overall survival was significantly improved for STRIDE versus sorafenib (hazard ratio; P = .0035). Median overall survival was 16.4 months for the STRIDE group versus 13.8 months for sorafenib and 16.6 months for durvalumab alone.

Median progression-free survival was 3.8 months, 3.7 months, and 41.1 months, respectively.

The overall response rate for the STRIDE arm was 20.1% compared to 17% for durvalumab, and 5.1% for sorafenib, and the median duration of response was 22.3 months, 16.8 months, and 18.4 months, respectively.

Treatment-related grade 3 or 4 adverse events occurred in 25.8% of patients on the combination, compared with 12.9% for durvalumab and 36.9% for sorafenib.

Grade 5 events occurred in 2.3% of the STRIDE group, compared with 0% among those receiving durvalumab alone and 0.8% in the sorafenib group. Treatment discontinuation due to events occurred in 8.2%, 4.1%, and 11.0% of patients, respectively.
 

New option for first-line treatment

In his discussion of the abstract, Dr. El-Khoueiry raised a few issues with the HIMALAYA trial that he felt needed further investigation.

Due to the study design, no conclusions can be drawn regarding the STRIDE regimen versus durvalumab as a single agent – the study was not powered for that, he said.

Also, the trial excluded patients with main portal vein thrombosis (PVT), he noted, and he felt that the subgroup analysis of hepatitis C patients requires further study.

“Another point is that, compared with other studies, bleeding events were less common in the HIMALAYA trial, but it did exclude patients with main PVT who are at highest risk of bleeding,” he pointed out.

STRIDE has a different toxicity profile from that seen with VEGF-containing combinations (for example, containing bevacizumab) and has a lower bleeding risk and a manageable rate of immune-mediated adverse events that require steroids. “But looking at non-VEGF regimens, is there an advantage to this, since most subsequent therapies target VEGF?” he questioned.

Another question is if there is a role for single agent PD-1/PD-L1 in first-line HCC. “This trial found that durvalumab was noninferior to sorafenib. This could be a first-line treatment option for select patients – maybe those who are poor candidates for combination therapy or have contraindications to VEGF,” said Dr. El-Khoueiry.

Nevertheless, STRIDE represents an emerging treatment option for this population, especially for patients who have contraindications for bevacizumab and a high bleeding risk, he concluded.

“So for HCC, it is amazing that we now have multiple first-line treatment options available,” he said. “The choice of therapy should be guided by toxicity profile and patient specific contraindications.”

For the future, he emphasized that biomarker development is critical to enhance a personalized approach driven by tumor and host biology.

“Sorafenib is no longer an appropriate control arm for first-line trials,” he said. “Timing of transition from liver-directed therapy to systemic therapy is critical given multiple available options.”

HCC in the setting of compromised liver function continues to be an unmet need. “And finally, in the second line and beyond, therapy after first-line immunotherapy combinations is largely empiric,” he said. “Research is needed to establish the efficacy of available and future therapeutic options post immunotherapy and the optimal sequence.”

This study received funding from AstraZeneca, maker of durvalumab. Dr. Abou-Alfa and Dr. El-Khoueiry reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

A novel dual immunotherapy regimen significantly improved overall survival compared to a standard of care in patients with advanced, unresectable hepatocellular carcinoma (HCC) in the large phase 3 HIMALAYA trial.

The novel regimen, dubbed STRIDE (Single T Regular Interval D), comprised a single priming dose of the investigational agent tremelimumab followed by regular doses of durvalumab (Imfinzi).

Patients on this regimen experienced a 22% lower risk of death than patients treated with sorafenib (Nexavar), which at the time the trial began was the only approved frontline standard of care for patients with advanced HCC.

At 3 years, almost 31% of patients treated with combination therapy were still alive, versus 24.7% for durvalumab alone and 20.2% for sorafenib.

This novel regimen “may represent new treatment options for patients with untreated hepatocellular carcinoma,” said lead author Ghassan Abou-Alfa, MD, MBA, an attending physician at Memorial Sloan Kettering Comprehensive Cancer Center, New York. “Pending FDA approval, this novel dual immunotherapy regimen could be readily available to all patients and would not require additional safety assessments prior to treatment.”

He presented the new results here at the Gastrointestinal Cancers Symposium (GICS) 2022.

Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, agreed that the STRIDE regimen, with the combination of one priming dose of tremelimumab and regular interval durvalumab, is a new first-line treatment option for advanced HCC patients.

“But there are some limitations to the study and topics that will require further additional investigation,” he added.
 

Liver cancer increasing

Liver cancer is one of the few cancers for which deaths rates are increasing. In the United States. The overall rate of death due to liver cancer has doubled since 1980, Dr. Abou-Alfa told the audience. The most recent 5-year survival rates are 32.6% for localized disease, 10.8% with regional disease, and 2.4% with distant disease.

Until recently, first-line treatment for untreated HCC was limited to the multikinase inhibitors sorafenib and lenvatinib (Lenvima), which have been associated with median overall survival of approximately 1 year but also with toxicities that impact the quality of life, he commented.

“More recently, the anti-PD-L1 agent atezolizumab plus bevacizumab showed significant survival benefit versus sorafenib and have become a standard of care following approval in 2020,” Dr. Abou-Alfa said.

Tremelimumab is an experimental immunotherapy that targets the CTLA-4 receptor, and in 2020 it received orphan drug status for the treatment of HCC from the U.S. Food and Drug Administration. The authors hypothesized that tremelimumab would boost the response to durvalumab, a PDL-1 inhibitor, as this had been observed in the phase 2 Study 22 trial, which had tested the STRIDE regimen.

Now in the phase 3 HIMALAYA trial, the STRIDE regimen was compared to durvalumab used alone and to sorafenib used alone.

The trial randomized 1,171 patients to receive either the STRIDE regimen (a single dose of 75 mg tremelimumab plus 1,500 mg durvalumab every 4 weeks) or durvalumab alone (1,500 mg every 4 weeks) or sorafenib alone (400 mg twice daily).

Initially, there was also a lower-dose tremelimumab-containing arm, but recruitment into this arm was halted after a planned analysis of Study 22 failed to show a meaningful efficacy difference between that arm and durvalumab alone.

At data cutoff, the study’s primary objective was met. Overall survival was significantly improved for STRIDE versus sorafenib (hazard ratio; P = .0035). Median overall survival was 16.4 months for the STRIDE group versus 13.8 months for sorafenib and 16.6 months for durvalumab alone.

Median progression-free survival was 3.8 months, 3.7 months, and 41.1 months, respectively.

The overall response rate for the STRIDE arm was 20.1% compared to 17% for durvalumab, and 5.1% for sorafenib, and the median duration of response was 22.3 months, 16.8 months, and 18.4 months, respectively.

Treatment-related grade 3 or 4 adverse events occurred in 25.8% of patients on the combination, compared with 12.9% for durvalumab and 36.9% for sorafenib.

Grade 5 events occurred in 2.3% of the STRIDE group, compared with 0% among those receiving durvalumab alone and 0.8% in the sorafenib group. Treatment discontinuation due to events occurred in 8.2%, 4.1%, and 11.0% of patients, respectively.
 

New option for first-line treatment

In his discussion of the abstract, Dr. El-Khoueiry raised a few issues with the HIMALAYA trial that he felt needed further investigation.

Due to the study design, no conclusions can be drawn regarding the STRIDE regimen versus durvalumab as a single agent – the study was not powered for that, he said.

Also, the trial excluded patients with main portal vein thrombosis (PVT), he noted, and he felt that the subgroup analysis of hepatitis C patients requires further study.

“Another point is that, compared with other studies, bleeding events were less common in the HIMALAYA trial, but it did exclude patients with main PVT who are at highest risk of bleeding,” he pointed out.

STRIDE has a different toxicity profile from that seen with VEGF-containing combinations (for example, containing bevacizumab) and has a lower bleeding risk and a manageable rate of immune-mediated adverse events that require steroids. “But looking at non-VEGF regimens, is there an advantage to this, since most subsequent therapies target VEGF?” he questioned.

Another question is if there is a role for single agent PD-1/PD-L1 in first-line HCC. “This trial found that durvalumab was noninferior to sorafenib. This could be a first-line treatment option for select patients – maybe those who are poor candidates for combination therapy or have contraindications to VEGF,” said Dr. El-Khoueiry.

Nevertheless, STRIDE represents an emerging treatment option for this population, especially for patients who have contraindications for bevacizumab and a high bleeding risk, he concluded.

“So for HCC, it is amazing that we now have multiple first-line treatment options available,” he said. “The choice of therapy should be guided by toxicity profile and patient specific contraindications.”

For the future, he emphasized that biomarker development is critical to enhance a personalized approach driven by tumor and host biology.

“Sorafenib is no longer an appropriate control arm for first-line trials,” he said. “Timing of transition from liver-directed therapy to systemic therapy is critical given multiple available options.”

HCC in the setting of compromised liver function continues to be an unmet need. “And finally, in the second line and beyond, therapy after first-line immunotherapy combinations is largely empiric,” he said. “Research is needed to establish the efficacy of available and future therapeutic options post immunotherapy and the optimal sequence.”

This study received funding from AstraZeneca, maker of durvalumab. Dr. Abou-Alfa and Dr. El-Khoueiry reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

A novel dual immunotherapy regimen significantly improved overall survival compared to a standard of care in patients with advanced, unresectable hepatocellular carcinoma (HCC) in the large phase 3 HIMALAYA trial.

The novel regimen, dubbed STRIDE (Single T Regular Interval D), comprised a single priming dose of the investigational agent tremelimumab followed by regular doses of durvalumab (Imfinzi).

Patients on this regimen experienced a 22% lower risk of death than patients treated with sorafenib (Nexavar), which at the time the trial began was the only approved frontline standard of care for patients with advanced HCC.

At 3 years, almost 31% of patients treated with combination therapy were still alive, versus 24.7% for durvalumab alone and 20.2% for sorafenib.

This novel regimen “may represent new treatment options for patients with untreated hepatocellular carcinoma,” said lead author Ghassan Abou-Alfa, MD, MBA, an attending physician at Memorial Sloan Kettering Comprehensive Cancer Center, New York. “Pending FDA approval, this novel dual immunotherapy regimen could be readily available to all patients and would not require additional safety assessments prior to treatment.”

He presented the new results here at the Gastrointestinal Cancers Symposium (GICS) 2022.

Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, agreed that the STRIDE regimen, with the combination of one priming dose of tremelimumab and regular interval durvalumab, is a new first-line treatment option for advanced HCC patients.

“But there are some limitations to the study and topics that will require further additional investigation,” he added.
 

Liver cancer increasing

Liver cancer is one of the few cancers for which deaths rates are increasing. In the United States. The overall rate of death due to liver cancer has doubled since 1980, Dr. Abou-Alfa told the audience. The most recent 5-year survival rates are 32.6% for localized disease, 10.8% with regional disease, and 2.4% with distant disease.

Until recently, first-line treatment for untreated HCC was limited to the multikinase inhibitors sorafenib and lenvatinib (Lenvima), which have been associated with median overall survival of approximately 1 year but also with toxicities that impact the quality of life, he commented.

“More recently, the anti-PD-L1 agent atezolizumab plus bevacizumab showed significant survival benefit versus sorafenib and have become a standard of care following approval in 2020,” Dr. Abou-Alfa said.

Tremelimumab is an experimental immunotherapy that targets the CTLA-4 receptor, and in 2020 it received orphan drug status for the treatment of HCC from the U.S. Food and Drug Administration. The authors hypothesized that tremelimumab would boost the response to durvalumab, a PDL-1 inhibitor, as this had been observed in the phase 2 Study 22 trial, which had tested the STRIDE regimen.

Now in the phase 3 HIMALAYA trial, the STRIDE regimen was compared to durvalumab used alone and to sorafenib used alone.

The trial randomized 1,171 patients to receive either the STRIDE regimen (a single dose of 75 mg tremelimumab plus 1,500 mg durvalumab every 4 weeks) or durvalumab alone (1,500 mg every 4 weeks) or sorafenib alone (400 mg twice daily).

Initially, there was also a lower-dose tremelimumab-containing arm, but recruitment into this arm was halted after a planned analysis of Study 22 failed to show a meaningful efficacy difference between that arm and durvalumab alone.

At data cutoff, the study’s primary objective was met. Overall survival was significantly improved for STRIDE versus sorafenib (hazard ratio; P = .0035). Median overall survival was 16.4 months for the STRIDE group versus 13.8 months for sorafenib and 16.6 months for durvalumab alone.

Median progression-free survival was 3.8 months, 3.7 months, and 41.1 months, respectively.

The overall response rate for the STRIDE arm was 20.1% compared to 17% for durvalumab, and 5.1% for sorafenib, and the median duration of response was 22.3 months, 16.8 months, and 18.4 months, respectively.

Treatment-related grade 3 or 4 adverse events occurred in 25.8% of patients on the combination, compared with 12.9% for durvalumab and 36.9% for sorafenib.

Grade 5 events occurred in 2.3% of the STRIDE group, compared with 0% among those receiving durvalumab alone and 0.8% in the sorafenib group. Treatment discontinuation due to events occurred in 8.2%, 4.1%, and 11.0% of patients, respectively.
 

New option for first-line treatment

In his discussion of the abstract, Dr. El-Khoueiry raised a few issues with the HIMALAYA trial that he felt needed further investigation.

Due to the study design, no conclusions can be drawn regarding the STRIDE regimen versus durvalumab as a single agent – the study was not powered for that, he said.

Also, the trial excluded patients with main portal vein thrombosis (PVT), he noted, and he felt that the subgroup analysis of hepatitis C patients requires further study.

“Another point is that, compared with other studies, bleeding events were less common in the HIMALAYA trial, but it did exclude patients with main PVT who are at highest risk of bleeding,” he pointed out.

STRIDE has a different toxicity profile from that seen with VEGF-containing combinations (for example, containing bevacizumab) and has a lower bleeding risk and a manageable rate of immune-mediated adverse events that require steroids. “But looking at non-VEGF regimens, is there an advantage to this, since most subsequent therapies target VEGF?” he questioned.

Another question is if there is a role for single agent PD-1/PD-L1 in first-line HCC. “This trial found that durvalumab was noninferior to sorafenib. This could be a first-line treatment option for select patients – maybe those who are poor candidates for combination therapy or have contraindications to VEGF,” said Dr. El-Khoueiry.

Nevertheless, STRIDE represents an emerging treatment option for this population, especially for patients who have contraindications for bevacizumab and a high bleeding risk, he concluded.

“So for HCC, it is amazing that we now have multiple first-line treatment options available,” he said. “The choice of therapy should be guided by toxicity profile and patient specific contraindications.”

For the future, he emphasized that biomarker development is critical to enhance a personalized approach driven by tumor and host biology.

“Sorafenib is no longer an appropriate control arm for first-line trials,” he said. “Timing of transition from liver-directed therapy to systemic therapy is critical given multiple available options.”

HCC in the setting of compromised liver function continues to be an unmet need. “And finally, in the second line and beyond, therapy after first-line immunotherapy combinations is largely empiric,” he said. “Research is needed to establish the efficacy of available and future therapeutic options post immunotherapy and the optimal sequence.”

This study received funding from AstraZeneca, maker of durvalumab. Dr. Abou-Alfa and Dr. El-Khoueiry reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Adding transarterial chemoembolization (TACE) to treatment with lenvatinib (Lenvima) significantly improved survival, compared with lenvatinib alone in patients with advanced hepatocellular carcinoma (HCC) in the phase 3 LAUNCH trial.

The combination of TACE and lenvatinib “represents a potential new first-line treatment option for patients with advanced HCC,” said study author Ming Kuang, MD, PhD, professor in hepatobiliary surgery and interventional ultrasound and director of the cancer center in the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

The combination of the two approaches was “safe and effective for patients with advanced hepatocellular carcinoma and demonstrated remarkable improvements in overall survival, progression-free survival, and overall response rate, as well as acceptable toxicity,” he said.

Patients receiving combination therapy achieved a median overall survival of 17.8 months, compared with 11.5 months in the lenvatinib arm (hazard ratio, 0.45; P < .001). Similarly, median progression-free survival also favored lenvatinib plus TACE: 10.6 months vs. 6.4 months (HR, 0.43; P < .001).

The study results were presented at the Gastrointestinal Cancers Symposium.

Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, said the results are “intriguing,” and he commended the researchers on carrying out this study.

“It reinforces the feasibility of combined liver directed and systemic therapy,” he said.

“However, it does not change the standard of care in the U.S.,” he cautioned.

“Systemic therapy backbone is not the standard of care, and the design of this study was not optimal to answer the question of whether the addition of liver-directed therapy in advanced HCC improves outcomes,” he added.

Dr. EL-Khoueiry pointed out that these new results from the LAUNCH trial contrast with two studies that looked at liver-directed plus a systemic therapy. Both of those previous studies used sorafenib, one utilizing Y-90 and the other conventional TACE.

Both of those studies were negative, he said. “But there were differences between these studies and LAUNCH.”

Aside from the fact that they used sorafenib and not lenvatinib, another difference was that the patient population of LAUNCH was younger than in the other two studies. In addition, most patients in the LAUCH trial had hepatitis B, and they received a higher number of TACE treatments than in the previous studies. “One can argue that maybe treatment selection was more optimal,” Dr. El-Khoueiry commented.

He also noted that “the control arm of lenvatinib underperformed, as sorafenib median overall survival in previous trials ranges from 13 to 15 months. We would have expected lenvatinib to perform at least as well or better.” (The median overall survival was 11.5 months).
 

Improved outcomes with combination therapy

The LAUNCH study involved 338 treatment-naive patients with advanced HCC from 12 hospitals in China who were randomly assigned to receive either lenvatinib plus TACE (n = 170) or lenvatinib alone (n = 168).

TACE was administered on day 1 following treatment with lenvatinib, which was administered at 8 mg or 12 mg once daily, depending on the patient’s weight.

The majority of patients were 60 years of age or younger, with a median age of 54-56 years. The majority of patients were male (81.8% in the combination group vs. 78.6% in the lenvatinib-alone group), and the majority had hepatitis B (87.1% vs. 85.7%).

At a median follow-up of 18.4 months for the lenvatinib-TACE group and 17.0 months for the lenvatinib group, the results showed a significantly improved overall survival of 17.8 months with the combination vs. 11.5 months for monotherapy (HR, 0.45; P < .001). Median progression-free survival (PFS) was also significantly longer, at 10.6 months vs. 6.4 months, respectively (HR, 0.43; P < .001).

The overall response rate was 54.1% vs. 25.0% (P < .001), and one complete response was observed in each study arm. The complete response rate was 2.9% vs. 0.6%; partial response rate, 51.2% vs. 24.4%; stable disease rate, 40.0% vs. 48.2%; and rate of disease progression, 5.9% vs. 26.8% for the lenvatinib-TACE group and lenvatinib monotherapy groups. The disease control rate was 94.1% vs. 73.2%.

Grade 3-4 adverse events that occurred more frequently in the lenvatinib-TACE group than in the lenvatinib group included increased liver enzymes, with increased ALT in 17.6% vs. 1.2%; increased AST in 22.9% vs. 1.8%; and hyperbilirubinemia in 9.4% vs. 3.0%.

“Subgroup analysis shows that the combination group had better overall survival and progression-free survival in most of the analyzed subgroups,” said Dr. Kuang. “Multivariate analysis also found that portal vein tumor thrombus and treatment allocation were independent risk factors of overall survival, and that age, portal vein tumor thrombus, and treatment allocation were independent risk factors of progression-free survival.”
 

Study limitations

In his discussion of the abstract, Dr. El-Khoueiry noted that the LAUNCH trial had several limitations, one being the heterogeneity of the patient population and potential imbalance. “There is limited information regarding extrahepatic disease burden and distribution,” he explained. “Another limitation is that the younger population – with the majority having hepatitis B – limits the broad applicability of the result and has a potential impact on the low rate of treatment discontinuation.”

This study received no industry funding. Dr. Kuang has disclosed no relevant financial relationships. Dr. El-Khoueiry reported relationships with ABL bio, Agenus, Astex, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, CytomX Therapeutics, Eisai, EMD Serono, Exelixis, Fulgent Genetics, Gilead Sciences, Merck, Pieris Pharmaceuticals, QED Therapeutics, and Roche/Genentech.

A version of this article first appeared on Medscape.com.

Adding transarterial chemoembolization (TACE) to treatment with lenvatinib (Lenvima) significantly improved survival, compared with lenvatinib alone in patients with advanced hepatocellular carcinoma (HCC) in the phase 3 LAUNCH trial.

The combination of TACE and lenvatinib “represents a potential new first-line treatment option for patients with advanced HCC,” said study author Ming Kuang, MD, PhD, professor in hepatobiliary surgery and interventional ultrasound and director of the cancer center in the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

The combination of the two approaches was “safe and effective for patients with advanced hepatocellular carcinoma and demonstrated remarkable improvements in overall survival, progression-free survival, and overall response rate, as well as acceptable toxicity,” he said.

Patients receiving combination therapy achieved a median overall survival of 17.8 months, compared with 11.5 months in the lenvatinib arm (hazard ratio, 0.45; P < .001). Similarly, median progression-free survival also favored lenvatinib plus TACE: 10.6 months vs. 6.4 months (HR, 0.43; P < .001).

The study results were presented at the Gastrointestinal Cancers Symposium.

Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, said the results are “intriguing,” and he commended the researchers on carrying out this study.

“It reinforces the feasibility of combined liver directed and systemic therapy,” he said.

“However, it does not change the standard of care in the U.S.,” he cautioned.

“Systemic therapy backbone is not the standard of care, and the design of this study was not optimal to answer the question of whether the addition of liver-directed therapy in advanced HCC improves outcomes,” he added.

Dr. EL-Khoueiry pointed out that these new results from the LAUNCH trial contrast with two studies that looked at liver-directed plus a systemic therapy. Both of those previous studies used sorafenib, one utilizing Y-90 and the other conventional TACE.

Both of those studies were negative, he said. “But there were differences between these studies and LAUNCH.”

Aside from the fact that they used sorafenib and not lenvatinib, another difference was that the patient population of LAUNCH was younger than in the other two studies. In addition, most patients in the LAUCH trial had hepatitis B, and they received a higher number of TACE treatments than in the previous studies. “One can argue that maybe treatment selection was more optimal,” Dr. El-Khoueiry commented.

He also noted that “the control arm of lenvatinib underperformed, as sorafenib median overall survival in previous trials ranges from 13 to 15 months. We would have expected lenvatinib to perform at least as well or better.” (The median overall survival was 11.5 months).
 

Improved outcomes with combination therapy

The LAUNCH study involved 338 treatment-naive patients with advanced HCC from 12 hospitals in China who were randomly assigned to receive either lenvatinib plus TACE (n = 170) or lenvatinib alone (n = 168).

TACE was administered on day 1 following treatment with lenvatinib, which was administered at 8 mg or 12 mg once daily, depending on the patient’s weight.

The majority of patients were 60 years of age or younger, with a median age of 54-56 years. The majority of patients were male (81.8% in the combination group vs. 78.6% in the lenvatinib-alone group), and the majority had hepatitis B (87.1% vs. 85.7%).

At a median follow-up of 18.4 months for the lenvatinib-TACE group and 17.0 months for the lenvatinib group, the results showed a significantly improved overall survival of 17.8 months with the combination vs. 11.5 months for monotherapy (HR, 0.45; P < .001). Median progression-free survival (PFS) was also significantly longer, at 10.6 months vs. 6.4 months, respectively (HR, 0.43; P < .001).

The overall response rate was 54.1% vs. 25.0% (P < .001), and one complete response was observed in each study arm. The complete response rate was 2.9% vs. 0.6%; partial response rate, 51.2% vs. 24.4%; stable disease rate, 40.0% vs. 48.2%; and rate of disease progression, 5.9% vs. 26.8% for the lenvatinib-TACE group and lenvatinib monotherapy groups. The disease control rate was 94.1% vs. 73.2%.

Grade 3-4 adverse events that occurred more frequently in the lenvatinib-TACE group than in the lenvatinib group included increased liver enzymes, with increased ALT in 17.6% vs. 1.2%; increased AST in 22.9% vs. 1.8%; and hyperbilirubinemia in 9.4% vs. 3.0%.

“Subgroup analysis shows that the combination group had better overall survival and progression-free survival in most of the analyzed subgroups,” said Dr. Kuang. “Multivariate analysis also found that portal vein tumor thrombus and treatment allocation were independent risk factors of overall survival, and that age, portal vein tumor thrombus, and treatment allocation were independent risk factors of progression-free survival.”
 

Study limitations

In his discussion of the abstract, Dr. El-Khoueiry noted that the LAUNCH trial had several limitations, one being the heterogeneity of the patient population and potential imbalance. “There is limited information regarding extrahepatic disease burden and distribution,” he explained. “Another limitation is that the younger population – with the majority having hepatitis B – limits the broad applicability of the result and has a potential impact on the low rate of treatment discontinuation.”

This study received no industry funding. Dr. Kuang has disclosed no relevant financial relationships. Dr. El-Khoueiry reported relationships with ABL bio, Agenus, Astex, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, CytomX Therapeutics, Eisai, EMD Serono, Exelixis, Fulgent Genetics, Gilead Sciences, Merck, Pieris Pharmaceuticals, QED Therapeutics, and Roche/Genentech.

A version of this article first appeared on Medscape.com.

Adding transarterial chemoembolization (TACE) to treatment with lenvatinib (Lenvima) significantly improved survival, compared with lenvatinib alone in patients with advanced hepatocellular carcinoma (HCC) in the phase 3 LAUNCH trial.

The combination of TACE and lenvatinib “represents a potential new first-line treatment option for patients with advanced HCC,” said study author Ming Kuang, MD, PhD, professor in hepatobiliary surgery and interventional ultrasound and director of the cancer center in the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

The combination of the two approaches was “safe and effective for patients with advanced hepatocellular carcinoma and demonstrated remarkable improvements in overall survival, progression-free survival, and overall response rate, as well as acceptable toxicity,” he said.

Patients receiving combination therapy achieved a median overall survival of 17.8 months, compared with 11.5 months in the lenvatinib arm (hazard ratio, 0.45; P < .001). Similarly, median progression-free survival also favored lenvatinib plus TACE: 10.6 months vs. 6.4 months (HR, 0.43; P < .001).

The study results were presented at the Gastrointestinal Cancers Symposium.

Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, said the results are “intriguing,” and he commended the researchers on carrying out this study.

“It reinforces the feasibility of combined liver directed and systemic therapy,” he said.

“However, it does not change the standard of care in the U.S.,” he cautioned.

“Systemic therapy backbone is not the standard of care, and the design of this study was not optimal to answer the question of whether the addition of liver-directed therapy in advanced HCC improves outcomes,” he added.

Dr. EL-Khoueiry pointed out that these new results from the LAUNCH trial contrast with two studies that looked at liver-directed plus a systemic therapy. Both of those previous studies used sorafenib, one utilizing Y-90 and the other conventional TACE.

Both of those studies were negative, he said. “But there were differences between these studies and LAUNCH.”

Aside from the fact that they used sorafenib and not lenvatinib, another difference was that the patient population of LAUNCH was younger than in the other two studies. In addition, most patients in the LAUCH trial had hepatitis B, and they received a higher number of TACE treatments than in the previous studies. “One can argue that maybe treatment selection was more optimal,” Dr. El-Khoueiry commented.

He also noted that “the control arm of lenvatinib underperformed, as sorafenib median overall survival in previous trials ranges from 13 to 15 months. We would have expected lenvatinib to perform at least as well or better.” (The median overall survival was 11.5 months).
 

Improved outcomes with combination therapy

The LAUNCH study involved 338 treatment-naive patients with advanced HCC from 12 hospitals in China who were randomly assigned to receive either lenvatinib plus TACE (n = 170) or lenvatinib alone (n = 168).

TACE was administered on day 1 following treatment with lenvatinib, which was administered at 8 mg or 12 mg once daily, depending on the patient’s weight.

The majority of patients were 60 years of age or younger, with a median age of 54-56 years. The majority of patients were male (81.8% in the combination group vs. 78.6% in the lenvatinib-alone group), and the majority had hepatitis B (87.1% vs. 85.7%).

At a median follow-up of 18.4 months for the lenvatinib-TACE group and 17.0 months for the lenvatinib group, the results showed a significantly improved overall survival of 17.8 months with the combination vs. 11.5 months for monotherapy (HR, 0.45; P < .001). Median progression-free survival (PFS) was also significantly longer, at 10.6 months vs. 6.4 months, respectively (HR, 0.43; P < .001).

The overall response rate was 54.1% vs. 25.0% (P < .001), and one complete response was observed in each study arm. The complete response rate was 2.9% vs. 0.6%; partial response rate, 51.2% vs. 24.4%; stable disease rate, 40.0% vs. 48.2%; and rate of disease progression, 5.9% vs. 26.8% for the lenvatinib-TACE group and lenvatinib monotherapy groups. The disease control rate was 94.1% vs. 73.2%.

Grade 3-4 adverse events that occurred more frequently in the lenvatinib-TACE group than in the lenvatinib group included increased liver enzymes, with increased ALT in 17.6% vs. 1.2%; increased AST in 22.9% vs. 1.8%; and hyperbilirubinemia in 9.4% vs. 3.0%.

“Subgroup analysis shows that the combination group had better overall survival and progression-free survival in most of the analyzed subgroups,” said Dr. Kuang. “Multivariate analysis also found that portal vein tumor thrombus and treatment allocation were independent risk factors of overall survival, and that age, portal vein tumor thrombus, and treatment allocation were independent risk factors of progression-free survival.”
 

Study limitations

In his discussion of the abstract, Dr. El-Khoueiry noted that the LAUNCH trial had several limitations, one being the heterogeneity of the patient population and potential imbalance. “There is limited information regarding extrahepatic disease burden and distribution,” he explained. “Another limitation is that the younger population – with the majority having hepatitis B – limits the broad applicability of the result and has a potential impact on the low rate of treatment discontinuation.”

This study received no industry funding. Dr. Kuang has disclosed no relevant financial relationships. Dr. El-Khoueiry reported relationships with ABL bio, Agenus, Astex, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, CytomX Therapeutics, Eisai, EMD Serono, Exelixis, Fulgent Genetics, Gilead Sciences, Merck, Pieris Pharmaceuticals, QED Therapeutics, and Roche/Genentech.

A version of this article first appeared on Medscape.com.

Oncologists were less likely than many other specialists to be named in malpractice suits during 2021, notes the latest Medscape Malpractice Report.

Over a third (39%) of oncologists who were surveyed said that they had been named in at least one malpractice suit, according to the Medscape Oncologist Malpractice Report 2021.

Jupiterimages/ThinkStock

This number is considerably lower than that reported by physicians across all specialties (51%), and it is also much lower than that reported by oncologists in past years. In the 2019 report, 54% of oncologists surveyed said they had been named in a malpractice suit, while in the 2017 report, the figure was 53%.

The dramatic decline in malpractice suits may have much to do with the COVID-19 pandemic, when oncology care was in a state of flux.

“Fewer people were seeking cancer care during the COVID pandemic, which might have impacted the number of lawsuits brought against oncologists,” says Paul Walker, a New York–based malpractice attorney at Walker Medical Law, who represents physicians and other healthcare professionals.

“Additionally, a fair number of people who died of COVID were also older,” he pointed out, and it is often older people who get cancer, so there were fewer older people who consulted an oncologist or were treated by one, he added.

However, the pandemic may be storing up trouble for future years. “Patient fears of contracting COVID-19 have led many to avoid seeking or resuming care, so delays in diagnosing new cancer cases could mean that more patients are diagnosed at a later stage of their disease, leading to potential adverse events and malpractice claims,” commented David L. Feldman, MD, MBA, chief medical officer of The Doctors Company Group.

This latest 2021 Medscape Malpractice Report was compiled from an online survey that included more than 4,300 physicians from 29 specialties. It included 106 oncologists. More than half of respondents (56%) had been in practice for more than 25 years, and 54% were aged 60 years or older. The survey was available from May 21 to August 28, 2021.

Similar to findings in previous years, complications from treatment/surgery were the most common reason for the lawsuits (31%). Failure to make a correct diagnosis or a delay in diagnosis was the second most common reason (23%), while 20% of patients sued because of a poor outcome or disease progression.
 

Surprise at being sued

Among the oncologists who reported involvement in a lawsuit in 2021, the majority (86%) said they were “very surprised” or “somewhat surprised” by the malpractice suit, which is similar to that of other physicians surveyed. However, fewer were surprised this year as compared to 2019 and 2017 (90% and 94%).

One reason for the surprise over the litigation was that it concerned a patient who had been treated a long time ago. One oncologist wrote that “the patient had not seen me for over 7 years and during that time, he did not call me with his new symptomatology. I was only named in the suit because I had previously been involved.”

Another common scenario reported by oncologists was being named in a lawsuit which was brought by another clinician’s patient. “I was the chairperson of the department, and one of the doctors in the practice was involved in the suit,” wrote one respondent. “I was named as an accomplice.”

More than half of surveyed oncologists said that they were able to identify the patient who bought the suit, and these figures are again comparable to those of other physicians. One oncologist commented that in the case he was involved with, the family did not understand or accept the nature of cancer and the different ways that a patient could die of complications. This patient had died of sepsis and pneumonia related to decubitus ulcers that were completely unrelated to her radiation therapy.

As in the case above, sometimes it is the family who filed the lawsuit, not the patient.

“The patient may even recognize that you did your best and be grateful for your skill and efforts, but the family can’t accept that grandma died of cancer and brings a lawsuit,” said Dennis Hursh, an attorney with Physicians Agreement Health Law in Pennsylvania.

When looking at outcomes of the lawsuit, 40% of oncologists were dismissed from the suit within the first few months, or the case was settled before going to trial. This trend is also consistent with the results from the 2019 and 2017 surveys. When the case did go to trial, 10% received a favorable verdict, which was the same in 2019.

“It seems that most of my clients end up being released from lawsuits, and many lawsuits are dismissed prior to proceeding to trial,” Mr. Hursh commented.
 

Murdering psychopath

Some oncologists weighed in on what they felt was the worst experience of being sued.

“Mental anguish, knowing that I did nothing wrong,” said one physician. Another reported that it was a feeling of being “inadequate and totally alone.”

Another oncologist commented that the “depositions from lawyers implied that I was worse than a murdering psychopath. My reputation was permanently damaged.”

However, the vast majority of oncologists (88%) did not believe that the lawsuit negatively affected their career, which was similar to physicians in general. That said, many did complain about the ongoing requirement to report the lawsuit to the credentialing committee, even if it was dismissed, and then having to pay increased malpractice premiums. “I still need to document this episode every single time I apply for any medical position, even more than 29 years after I was dismissed from the case,” said one respondent.

When asked if they would do anything differently, many oncologists (42%) said no, they would not have done anything differently. This is similar to the responses from physicians in general and with 2019 responses from oncologists. However, 15% of the respondents said that in retrospect, they would not have taken on that patient to begin with.

Some oncologists noted that they would have been more conscientious in relaying the information to the referring physician. Evan Lyman, an associate attorney at Voute, Lohrfink, McAndrew, Meisner & Roberts, LLP, in White Plains, N.Y., pointed out that a common reason for lawsuits is a slip-up of communication between the specialist and the referring physician.

Oncologists who had been sued have some insights to offer to colleagues, should they find themselves in a similar situation.

“Only answer with short and precise statements,” wrote one oncologist. “Attend all the depositions as much as you can; they are more likely to fabricate or exaggerate if you are not sitting in the room.”

Another physician said to base “everything on the medical record and do not answer hypothetical questions.”

“Document all interactions with patients as if a jury will be reading them, word by word,” said one respondent.

As for the public or patients, oncologists had this message: “malpractice suits should be rarely launched and only when gross errors can be absolutely proven.”

Another oncologist pointed out that communication is key. “Speak to the physicians against whom you have distrust. Lots of things could be cleared by good communication.”

A version of this article first appeared on Medscape.com.

Oncologists were less likely than many other specialists to be named in malpractice suits during 2021, notes the latest Medscape Malpractice Report.

Over a third (39%) of oncologists who were surveyed said that they had been named in at least one malpractice suit, according to the Medscape Oncologist Malpractice Report 2021.

Jupiterimages/ThinkStock

This number is considerably lower than that reported by physicians across all specialties (51%), and it is also much lower than that reported by oncologists in past years. In the 2019 report, 54% of oncologists surveyed said they had been named in a malpractice suit, while in the 2017 report, the figure was 53%.

The dramatic decline in malpractice suits may have much to do with the COVID-19 pandemic, when oncology care was in a state of flux.

“Fewer people were seeking cancer care during the COVID pandemic, which might have impacted the number of lawsuits brought against oncologists,” says Paul Walker, a New York–based malpractice attorney at Walker Medical Law, who represents physicians and other healthcare professionals.

“Additionally, a fair number of people who died of COVID were also older,” he pointed out, and it is often older people who get cancer, so there were fewer older people who consulted an oncologist or were treated by one, he added.

However, the pandemic may be storing up trouble for future years. “Patient fears of contracting COVID-19 have led many to avoid seeking or resuming care, so delays in diagnosing new cancer cases could mean that more patients are diagnosed at a later stage of their disease, leading to potential adverse events and malpractice claims,” commented David L. Feldman, MD, MBA, chief medical officer of The Doctors Company Group.

This latest 2021 Medscape Malpractice Report was compiled from an online survey that included more than 4,300 physicians from 29 specialties. It included 106 oncologists. More than half of respondents (56%) had been in practice for more than 25 years, and 54% were aged 60 years or older. The survey was available from May 21 to August 28, 2021.

Similar to findings in previous years, complications from treatment/surgery were the most common reason for the lawsuits (31%). Failure to make a correct diagnosis or a delay in diagnosis was the second most common reason (23%), while 20% of patients sued because of a poor outcome or disease progression.
 

Surprise at being sued

Among the oncologists who reported involvement in a lawsuit in 2021, the majority (86%) said they were “very surprised” or “somewhat surprised” by the malpractice suit, which is similar to that of other physicians surveyed. However, fewer were surprised this year as compared to 2019 and 2017 (90% and 94%).

One reason for the surprise over the litigation was that it concerned a patient who had been treated a long time ago. One oncologist wrote that “the patient had not seen me for over 7 years and during that time, he did not call me with his new symptomatology. I was only named in the suit because I had previously been involved.”

Another common scenario reported by oncologists was being named in a lawsuit which was brought by another clinician’s patient. “I was the chairperson of the department, and one of the doctors in the practice was involved in the suit,” wrote one respondent. “I was named as an accomplice.”

More than half of surveyed oncologists said that they were able to identify the patient who bought the suit, and these figures are again comparable to those of other physicians. One oncologist commented that in the case he was involved with, the family did not understand or accept the nature of cancer and the different ways that a patient could die of complications. This patient had died of sepsis and pneumonia related to decubitus ulcers that were completely unrelated to her radiation therapy.

As in the case above, sometimes it is the family who filed the lawsuit, not the patient.

“The patient may even recognize that you did your best and be grateful for your skill and efforts, but the family can’t accept that grandma died of cancer and brings a lawsuit,” said Dennis Hursh, an attorney with Physicians Agreement Health Law in Pennsylvania.

When looking at outcomes of the lawsuit, 40% of oncologists were dismissed from the suit within the first few months, or the case was settled before going to trial. This trend is also consistent with the results from the 2019 and 2017 surveys. When the case did go to trial, 10% received a favorable verdict, which was the same in 2019.

“It seems that most of my clients end up being released from lawsuits, and many lawsuits are dismissed prior to proceeding to trial,” Mr. Hursh commented.
 

Murdering psychopath

Some oncologists weighed in on what they felt was the worst experience of being sued.

“Mental anguish, knowing that I did nothing wrong,” said one physician. Another reported that it was a feeling of being “inadequate and totally alone.”

Another oncologist commented that the “depositions from lawyers implied that I was worse than a murdering psychopath. My reputation was permanently damaged.”

However, the vast majority of oncologists (88%) did not believe that the lawsuit negatively affected their career, which was similar to physicians in general. That said, many did complain about the ongoing requirement to report the lawsuit to the credentialing committee, even if it was dismissed, and then having to pay increased malpractice premiums. “I still need to document this episode every single time I apply for any medical position, even more than 29 years after I was dismissed from the case,” said one respondent.

When asked if they would do anything differently, many oncologists (42%) said no, they would not have done anything differently. This is similar to the responses from physicians in general and with 2019 responses from oncologists. However, 15% of the respondents said that in retrospect, they would not have taken on that patient to begin with.

Some oncologists noted that they would have been more conscientious in relaying the information to the referring physician. Evan Lyman, an associate attorney at Voute, Lohrfink, McAndrew, Meisner & Roberts, LLP, in White Plains, N.Y., pointed out that a common reason for lawsuits is a slip-up of communication between the specialist and the referring physician.

Oncologists who had been sued have some insights to offer to colleagues, should they find themselves in a similar situation.

“Only answer with short and precise statements,” wrote one oncologist. “Attend all the depositions as much as you can; they are more likely to fabricate or exaggerate if you are not sitting in the room.”

Another physician said to base “everything on the medical record and do not answer hypothetical questions.”

“Document all interactions with patients as if a jury will be reading them, word by word,” said one respondent.

As for the public or patients, oncologists had this message: “malpractice suits should be rarely launched and only when gross errors can be absolutely proven.”

Another oncologist pointed out that communication is key. “Speak to the physicians against whom you have distrust. Lots of things could be cleared by good communication.”

A version of this article first appeared on Medscape.com.

Oncologists were less likely than many other specialists to be named in malpractice suits during 2021, notes the latest Medscape Malpractice Report.

Over a third (39%) of oncologists who were surveyed said that they had been named in at least one malpractice suit, according to the Medscape Oncologist Malpractice Report 2021.

Jupiterimages/ThinkStock

This number is considerably lower than that reported by physicians across all specialties (51%), and it is also much lower than that reported by oncologists in past years. In the 2019 report, 54% of oncologists surveyed said they had been named in a malpractice suit, while in the 2017 report, the figure was 53%.

The dramatic decline in malpractice suits may have much to do with the COVID-19 pandemic, when oncology care was in a state of flux.

“Fewer people were seeking cancer care during the COVID pandemic, which might have impacted the number of lawsuits brought against oncologists,” says Paul Walker, a New York–based malpractice attorney at Walker Medical Law, who represents physicians and other healthcare professionals.

“Additionally, a fair number of people who died of COVID were also older,” he pointed out, and it is often older people who get cancer, so there were fewer older people who consulted an oncologist or were treated by one, he added.

However, the pandemic may be storing up trouble for future years. “Patient fears of contracting COVID-19 have led many to avoid seeking or resuming care, so delays in diagnosing new cancer cases could mean that more patients are diagnosed at a later stage of their disease, leading to potential adverse events and malpractice claims,” commented David L. Feldman, MD, MBA, chief medical officer of The Doctors Company Group.

This latest 2021 Medscape Malpractice Report was compiled from an online survey that included more than 4,300 physicians from 29 specialties. It included 106 oncologists. More than half of respondents (56%) had been in practice for more than 25 years, and 54% were aged 60 years or older. The survey was available from May 21 to August 28, 2021.

Similar to findings in previous years, complications from treatment/surgery were the most common reason for the lawsuits (31%). Failure to make a correct diagnosis or a delay in diagnosis was the second most common reason (23%), while 20% of patients sued because of a poor outcome or disease progression.
 

Surprise at being sued

Among the oncologists who reported involvement in a lawsuit in 2021, the majority (86%) said they were “very surprised” or “somewhat surprised” by the malpractice suit, which is similar to that of other physicians surveyed. However, fewer were surprised this year as compared to 2019 and 2017 (90% and 94%).

One reason for the surprise over the litigation was that it concerned a patient who had been treated a long time ago. One oncologist wrote that “the patient had not seen me for over 7 years and during that time, he did not call me with his new symptomatology. I was only named in the suit because I had previously been involved.”

Another common scenario reported by oncologists was being named in a lawsuit which was brought by another clinician’s patient. “I was the chairperson of the department, and one of the doctors in the practice was involved in the suit,” wrote one respondent. “I was named as an accomplice.”

More than half of surveyed oncologists said that they were able to identify the patient who bought the suit, and these figures are again comparable to those of other physicians. One oncologist commented that in the case he was involved with, the family did not understand or accept the nature of cancer and the different ways that a patient could die of complications. This patient had died of sepsis and pneumonia related to decubitus ulcers that were completely unrelated to her radiation therapy.

As in the case above, sometimes it is the family who filed the lawsuit, not the patient.

“The patient may even recognize that you did your best and be grateful for your skill and efforts, but the family can’t accept that grandma died of cancer and brings a lawsuit,” said Dennis Hursh, an attorney with Physicians Agreement Health Law in Pennsylvania.

When looking at outcomes of the lawsuit, 40% of oncologists were dismissed from the suit within the first few months, or the case was settled before going to trial. This trend is also consistent with the results from the 2019 and 2017 surveys. When the case did go to trial, 10% received a favorable verdict, which was the same in 2019.

“It seems that most of my clients end up being released from lawsuits, and many lawsuits are dismissed prior to proceeding to trial,” Mr. Hursh commented.
 

Murdering psychopath

Some oncologists weighed in on what they felt was the worst experience of being sued.

“Mental anguish, knowing that I did nothing wrong,” said one physician. Another reported that it was a feeling of being “inadequate and totally alone.”

Another oncologist commented that the “depositions from lawyers implied that I was worse than a murdering psychopath. My reputation was permanently damaged.”

However, the vast majority of oncologists (88%) did not believe that the lawsuit negatively affected their career, which was similar to physicians in general. That said, many did complain about the ongoing requirement to report the lawsuit to the credentialing committee, even if it was dismissed, and then having to pay increased malpractice premiums. “I still need to document this episode every single time I apply for any medical position, even more than 29 years after I was dismissed from the case,” said one respondent.

When asked if they would do anything differently, many oncologists (42%) said no, they would not have done anything differently. This is similar to the responses from physicians in general and with 2019 responses from oncologists. However, 15% of the respondents said that in retrospect, they would not have taken on that patient to begin with.

Some oncologists noted that they would have been more conscientious in relaying the information to the referring physician. Evan Lyman, an associate attorney at Voute, Lohrfink, McAndrew, Meisner & Roberts, LLP, in White Plains, N.Y., pointed out that a common reason for lawsuits is a slip-up of communication between the specialist and the referring physician.

Oncologists who had been sued have some insights to offer to colleagues, should they find themselves in a similar situation.

“Only answer with short and precise statements,” wrote one oncologist. “Attend all the depositions as much as you can; they are more likely to fabricate or exaggerate if you are not sitting in the room.”

Another physician said to base “everything on the medical record and do not answer hypothetical questions.”

“Document all interactions with patients as if a jury will be reading them, word by word,” said one respondent.

As for the public or patients, oncologists had this message: “malpractice suits should be rarely launched and only when gross errors can be absolutely proven.”

Another oncologist pointed out that communication is key. “Speak to the physicians against whom you have distrust. Lots of things could be cleared by good communication.”

A version of this article first appeared on Medscape.com.

Pembrolizumab (Keytruda) plus chemotherapy should be considered the new first-line standard of care in advanced esophageal cancer, according to the final results of a large phase 3 study.

An interim analysis of the KEYNOTE-590 study, published in 2020, found that the combination of pembrolizumab and chemotherapy in the first-line setting proved superior to chemotherapy alone in all outcome measures.

The updated analysis, which adds 12 months of follow-up data, shows “first-line pembrolizumab plus chemotherapy continued to provide clinically meaningful benefits in all patients with locally advanced and metastatic esophageal cancer, including [gastroesophageal junction] adenocarcinoma,” said lead author Jean-Philippe Metges, MD, of the CHU Brest-Institut de Cancerologie et d’Hematologie ARPEGO Network, Brest, France.

Similar quality of life and safety data were also observed with pembrolizumab plus chemotherapy versus chemotherapy alone, Dr. Metges added.

“These longer-term data further support first-line pembrolizumab plus chemotherapy as a new standard of care in patients with locally advanced and metastatic esophageal cancer,” he said.

The updated analysis was presented at the 2022 Gastrointestinal Cancers Symposium.
 

Pembro for esophageal cancer

Pembrolizumab first received regulatory approval in 2019 as monotherapy in the second-line setting to treat recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus in tumors with programmed death–ligand 1 (PD-L1) expression.

In response to the interim KEYNOTE-590 data, the FDA expanded the indication in 2021, granting accelerated approval for pembrolizumab in combination with platinum and fluoropyrimidine-based chemotherapy in the first-line setting for patients who were not candidates for surgical resection or definitive chemoradiotherapy.

The updated KEYNOTE-590 data lend greater weight for the use of pembrolizumab plus chemotherapy as first-line standard of care in advanced esophageal cancer.

In the analysis, a total of 749 eligible patients with previously untreated locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC), adenocarcinoma, or Siewert type 1 esophagogastric junction adenocarcinoma, regardless of PD-L1 status, were randomly assigned (1:1) to pembrolizumab 200 mg or placebo plus 5-fluorouracil and cisplatin once every 3 weeks for up to 35 cycles.

The authors evaluated overall survival in all patients as well as subgroups including those with ESCC, ESCC PD-L1 combined positive score ≥10 tumors, and PD-L1 CPS ≥10 tumors. The research team also looked at progression-free survival in most groups and overall response rate, duration of response, safety, and health-related quality of life.

Treatment continued until progression, unacceptable toxicity, withdrawal, or until 2 years, with no crossover permitted.

At the median follow-up of 34.8 months, median overall survival was longer for all patients receiving the combination therapy (hazard ratio, 0.73) as well as patients with ESCC (HR, 0.73), ESCC CPS ≥10 (HR, 0.59), CPS ≥10 (HR, 0.64), and adenocarcinoma (HR, 0.73).

For progression-free survival, pembrolizumab plus chemotherapy was superior in all patients (HR, 0.64), the ESCC group (HR, 0.65), as well as the PD-L1 CPS ≥10 tumor group (HR, 0.51).

The 24-month overall survival in all patients was also notably higher for those receiving the combination therapy – 26.3% versus 16.1% – as was 24-month progression-free survival – 11.6% versus 3.3%.

The overall response rate was 45.0% in the combination group, with 25 complete responses (6.7%), versus 29.3% in the control group, with 9 complete responses (2.4%). The median duration of response was 8.3 months in the combination group versus 6.0 months in the chemotherapy group. About 20% of patients in the combination group had a response rate lasting 24 months or longer, compared with 6% who received chemotherapy alone.

As for safety, grade 3-5 drug-related adverse events were similar in both arms – 72% for the combination versus 68% for chemotherapy alone. However, more patients in the combination group discontinued treatment because of drug-related adverse events – 21% versus 12%.

No additional or surprise adverse events occurred with the longer follow-up, plus quality of life was comparable between groups, Dr. Metges noted.

Stefano Cascinu, MD, Università Vita-Salute, San Raffaele Hospital, Milan, who was not involved in the analysis, reiterated that this update confirms the findings from earlier analyses and shows a benefit across all subgroups.

“One of the most relevant findings was that 20% of patients were responding for more than 24 months,” he said. “It is also important that a similar quality of life was maintained.”

Although Dr. Cascinu emphasized that this is a landmark trial in advanced esophageal and gastric cancers, he indicated to several points that remain to be investigated. These include the reproducibility of the findings in common clinical situations – such as a patient with impaired performance status, malnutrition, or peritoneal involvement – as well as the role of PD-L1.

The efficacy of the combination therapy across all subgroups led to a wide FDA approval, though the European Medicines Agency limited its approval to patients with PD-L1 CPS ≥10 tumors.

“Even though all subgroups did well, patients with [PD-L1] CPS ≥10 did better,” said Dr. Cascinu. “[And] in reality, the benefit may only be driven by a specific subpopulation.”

Dr. Cascinu added: “PD-L1 may be a negative biomarker and may be informative about the magnitude of benefit. This may be useful to discuss with patients regarding the expected benefit [of this therapeutic option].”

The study was supported by Merck & Co. Dr. Metges reported receiving payment for travel, accommodations, expenses from Amgen, LEO Pharma, and MSD Oncology, and receiving honoraria from Bristol-Myers Squibb, Lilly, Novartis, Sanofi, and Syncore. Dr. Cascinu has disclosed honoraria from BMS, Lilly, MSD Oncology, and others, as well as a consulting or advisory role for many of these same manufacturers and serving on the speakers’ bureau of Lilly and SERVIER. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A version of this article first appeared on Medscape.com.

Pembrolizumab (Keytruda) plus chemotherapy should be considered the new first-line standard of care in advanced esophageal cancer, according to the final results of a large phase 3 study.

An interim analysis of the KEYNOTE-590 study, published in 2020, found that the combination of pembrolizumab and chemotherapy in the first-line setting proved superior to chemotherapy alone in all outcome measures.

The updated analysis, which adds 12 months of follow-up data, shows “first-line pembrolizumab plus chemotherapy continued to provide clinically meaningful benefits in all patients with locally advanced and metastatic esophageal cancer, including [gastroesophageal junction] adenocarcinoma,” said lead author Jean-Philippe Metges, MD, of the CHU Brest-Institut de Cancerologie et d’Hematologie ARPEGO Network, Brest, France.

Similar quality of life and safety data were also observed with pembrolizumab plus chemotherapy versus chemotherapy alone, Dr. Metges added.

“These longer-term data further support first-line pembrolizumab plus chemotherapy as a new standard of care in patients with locally advanced and metastatic esophageal cancer,” he said.

The updated analysis was presented at the 2022 Gastrointestinal Cancers Symposium.
 

Pembro for esophageal cancer

Pembrolizumab first received regulatory approval in 2019 as monotherapy in the second-line setting to treat recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus in tumors with programmed death–ligand 1 (PD-L1) expression.

In response to the interim KEYNOTE-590 data, the FDA expanded the indication in 2021, granting accelerated approval for pembrolizumab in combination with platinum and fluoropyrimidine-based chemotherapy in the first-line setting for patients who were not candidates for surgical resection or definitive chemoradiotherapy.

The updated KEYNOTE-590 data lend greater weight for the use of pembrolizumab plus chemotherapy as first-line standard of care in advanced esophageal cancer.

In the analysis, a total of 749 eligible patients with previously untreated locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC), adenocarcinoma, or Siewert type 1 esophagogastric junction adenocarcinoma, regardless of PD-L1 status, were randomly assigned (1:1) to pembrolizumab 200 mg or placebo plus 5-fluorouracil and cisplatin once every 3 weeks for up to 35 cycles.

The authors evaluated overall survival in all patients as well as subgroups including those with ESCC, ESCC PD-L1 combined positive score ≥10 tumors, and PD-L1 CPS ≥10 tumors. The research team also looked at progression-free survival in most groups and overall response rate, duration of response, safety, and health-related quality of life.

Treatment continued until progression, unacceptable toxicity, withdrawal, or until 2 years, with no crossover permitted.

At the median follow-up of 34.8 months, median overall survival was longer for all patients receiving the combination therapy (hazard ratio, 0.73) as well as patients with ESCC (HR, 0.73), ESCC CPS ≥10 (HR, 0.59), CPS ≥10 (HR, 0.64), and adenocarcinoma (HR, 0.73).

For progression-free survival, pembrolizumab plus chemotherapy was superior in all patients (HR, 0.64), the ESCC group (HR, 0.65), as well as the PD-L1 CPS ≥10 tumor group (HR, 0.51).

The 24-month overall survival in all patients was also notably higher for those receiving the combination therapy – 26.3% versus 16.1% – as was 24-month progression-free survival – 11.6% versus 3.3%.

The overall response rate was 45.0% in the combination group, with 25 complete responses (6.7%), versus 29.3% in the control group, with 9 complete responses (2.4%). The median duration of response was 8.3 months in the combination group versus 6.0 months in the chemotherapy group. About 20% of patients in the combination group had a response rate lasting 24 months or longer, compared with 6% who received chemotherapy alone.

As for safety, grade 3-5 drug-related adverse events were similar in both arms – 72% for the combination versus 68% for chemotherapy alone. However, more patients in the combination group discontinued treatment because of drug-related adverse events – 21% versus 12%.

No additional or surprise adverse events occurred with the longer follow-up, plus quality of life was comparable between groups, Dr. Metges noted.

Stefano Cascinu, MD, Università Vita-Salute, San Raffaele Hospital, Milan, who was not involved in the analysis, reiterated that this update confirms the findings from earlier analyses and shows a benefit across all subgroups.

“One of the most relevant findings was that 20% of patients were responding for more than 24 months,” he said. “It is also important that a similar quality of life was maintained.”

Although Dr. Cascinu emphasized that this is a landmark trial in advanced esophageal and gastric cancers, he indicated to several points that remain to be investigated. These include the reproducibility of the findings in common clinical situations – such as a patient with impaired performance status, malnutrition, or peritoneal involvement – as well as the role of PD-L1.

The efficacy of the combination therapy across all subgroups led to a wide FDA approval, though the European Medicines Agency limited its approval to patients with PD-L1 CPS ≥10 tumors.

“Even though all subgroups did well, patients with [PD-L1] CPS ≥10 did better,” said Dr. Cascinu. “[And] in reality, the benefit may only be driven by a specific subpopulation.”

Dr. Cascinu added: “PD-L1 may be a negative biomarker and may be informative about the magnitude of benefit. This may be useful to discuss with patients regarding the expected benefit [of this therapeutic option].”

The study was supported by Merck & Co. Dr. Metges reported receiving payment for travel, accommodations, expenses from Amgen, LEO Pharma, and MSD Oncology, and receiving honoraria from Bristol-Myers Squibb, Lilly, Novartis, Sanofi, and Syncore. Dr. Cascinu has disclosed honoraria from BMS, Lilly, MSD Oncology, and others, as well as a consulting or advisory role for many of these same manufacturers and serving on the speakers’ bureau of Lilly and SERVIER. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A version of this article first appeared on Medscape.com.

Pembrolizumab (Keytruda) plus chemotherapy should be considered the new first-line standard of care in advanced esophageal cancer, according to the final results of a large phase 3 study.

An interim analysis of the KEYNOTE-590 study, published in 2020, found that the combination of pembrolizumab and chemotherapy in the first-line setting proved superior to chemotherapy alone in all outcome measures.

The updated analysis, which adds 12 months of follow-up data, shows “first-line pembrolizumab plus chemotherapy continued to provide clinically meaningful benefits in all patients with locally advanced and metastatic esophageal cancer, including [gastroesophageal junction] adenocarcinoma,” said lead author Jean-Philippe Metges, MD, of the CHU Brest-Institut de Cancerologie et d’Hematologie ARPEGO Network, Brest, France.

Similar quality of life and safety data were also observed with pembrolizumab plus chemotherapy versus chemotherapy alone, Dr. Metges added.

“These longer-term data further support first-line pembrolizumab plus chemotherapy as a new standard of care in patients with locally advanced and metastatic esophageal cancer,” he said.

The updated analysis was presented at the 2022 Gastrointestinal Cancers Symposium.
 

Pembro for esophageal cancer

Pembrolizumab first received regulatory approval in 2019 as monotherapy in the second-line setting to treat recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus in tumors with programmed death–ligand 1 (PD-L1) expression.

In response to the interim KEYNOTE-590 data, the FDA expanded the indication in 2021, granting accelerated approval for pembrolizumab in combination with platinum and fluoropyrimidine-based chemotherapy in the first-line setting for patients who were not candidates for surgical resection or definitive chemoradiotherapy.

The updated KEYNOTE-590 data lend greater weight for the use of pembrolizumab plus chemotherapy as first-line standard of care in advanced esophageal cancer.

In the analysis, a total of 749 eligible patients with previously untreated locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC), adenocarcinoma, or Siewert type 1 esophagogastric junction adenocarcinoma, regardless of PD-L1 status, were randomly assigned (1:1) to pembrolizumab 200 mg or placebo plus 5-fluorouracil and cisplatin once every 3 weeks for up to 35 cycles.

The authors evaluated overall survival in all patients as well as subgroups including those with ESCC, ESCC PD-L1 combined positive score ≥10 tumors, and PD-L1 CPS ≥10 tumors. The research team also looked at progression-free survival in most groups and overall response rate, duration of response, safety, and health-related quality of life.

Treatment continued until progression, unacceptable toxicity, withdrawal, or until 2 years, with no crossover permitted.

At the median follow-up of 34.8 months, median overall survival was longer for all patients receiving the combination therapy (hazard ratio, 0.73) as well as patients with ESCC (HR, 0.73), ESCC CPS ≥10 (HR, 0.59), CPS ≥10 (HR, 0.64), and adenocarcinoma (HR, 0.73).

For progression-free survival, pembrolizumab plus chemotherapy was superior in all patients (HR, 0.64), the ESCC group (HR, 0.65), as well as the PD-L1 CPS ≥10 tumor group (HR, 0.51).

The 24-month overall survival in all patients was also notably higher for those receiving the combination therapy – 26.3% versus 16.1% – as was 24-month progression-free survival – 11.6% versus 3.3%.

The overall response rate was 45.0% in the combination group, with 25 complete responses (6.7%), versus 29.3% in the control group, with 9 complete responses (2.4%). The median duration of response was 8.3 months in the combination group versus 6.0 months in the chemotherapy group. About 20% of patients in the combination group had a response rate lasting 24 months or longer, compared with 6% who received chemotherapy alone.

As for safety, grade 3-5 drug-related adverse events were similar in both arms – 72% for the combination versus 68% for chemotherapy alone. However, more patients in the combination group discontinued treatment because of drug-related adverse events – 21% versus 12%.

No additional or surprise adverse events occurred with the longer follow-up, plus quality of life was comparable between groups, Dr. Metges noted.

Stefano Cascinu, MD, Università Vita-Salute, San Raffaele Hospital, Milan, who was not involved in the analysis, reiterated that this update confirms the findings from earlier analyses and shows a benefit across all subgroups.

“One of the most relevant findings was that 20% of patients were responding for more than 24 months,” he said. “It is also important that a similar quality of life was maintained.”

Although Dr. Cascinu emphasized that this is a landmark trial in advanced esophageal and gastric cancers, he indicated to several points that remain to be investigated. These include the reproducibility of the findings in common clinical situations – such as a patient with impaired performance status, malnutrition, or peritoneal involvement – as well as the role of PD-L1.

The efficacy of the combination therapy across all subgroups led to a wide FDA approval, though the European Medicines Agency limited its approval to patients with PD-L1 CPS ≥10 tumors.

“Even though all subgroups did well, patients with [PD-L1] CPS ≥10 did better,” said Dr. Cascinu. “[And] in reality, the benefit may only be driven by a specific subpopulation.”

Dr. Cascinu added: “PD-L1 may be a negative biomarker and may be informative about the magnitude of benefit. This may be useful to discuss with patients regarding the expected benefit [of this therapeutic option].”

The study was supported by Merck & Co. Dr. Metges reported receiving payment for travel, accommodations, expenses from Amgen, LEO Pharma, and MSD Oncology, and receiving honoraria from Bristol-Myers Squibb, Lilly, Novartis, Sanofi, and Syncore. Dr. Cascinu has disclosed honoraria from BMS, Lilly, MSD Oncology, and others, as well as a consulting or advisory role for many of these same manufacturers and serving on the speakers’ bureau of Lilly and SERVIER. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A version of this article first appeared on Medscape.com.

Adding the checkpoint inhibitor durvalumab (Imfinzi) to chemotherapy significantly improved overall survival in patients with advanced biliary tract cancer, as compared to chemotherapy alone, according to interim results from the TOPAZ-1 trial.

The risk of death for those taking durvalumab plus chemotherapy was 20% lower than for patients on chemotherapy alone. At 18 months, overall survival was 35.1% in the durvalumab group versus 25.6% for chemotherapy alone. By 2 years, overall survival was 24.9% versus 10.4%.

“TOPAZ-1 is the first phase 3 trial to show that adding immunotherapy to standard chemotherapy can increase survival in biliary tract cancer, and importantly, does so without inducing any new serious side effects,” said lead author Do-Youn Oh, MD, PhD, professor in the Division of Medical Oncology at Seoul National University Hospital and Seoul National University College of Medicine, Korea.

“The study met its primary endpoint at a prespecified interim analysis, and durvalumab plus gemcitabine and cisplatin demonstrated statistically significant and clinically meaningful prolonged overall survival compared with placebo plus chemotherapy,” she said.

“This is an effective first-line therapy and could become a new standard of care for patients with advanced biliary tract cancer,” she added.

Dr. Oh presented the results at the Gastrointestinal Cancers Symposium (GICS) 2022.

In a discussion of the paper, Nilofer Saba Azad, MD, from the department of oncology, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, noted that overall, “we are seeing enticing benefit in survival and response rate.”

“There is moderately strong preliminary clinical data and biological rationale that immune checkpoint may have some activity in biliary tract cancer,” she said. “The trial was adequately powered and accounted for important known clinical subsets, and [it] was placebo controlled. The results suggest a meaningful benefit for patients.”

However, she pointed out that there are still open questions, mostly having to do with the subgroup analysis.
 

Biliary tract cancer: Incidence is rising

Biliary tract cancers are a relatively rare and heterogeneous group of cancers, and global incidence is rising. “Advanced unresectable biliary tract cancer is an area of high unmet need due to its aggressive nature, limited treatment options, and poor prognosis,” explained Dr. Oh. “The first-line standard of care for advanced biliary tract cancers, gemcitabine and cisplatin, has remained unchanged for over a decade.”

Previous research has suggested that checkpoint inhibition may result in antitumor immune responses, she commented. A previous phase 2 trial showed that durvalumab combined with gemcitabine and cisplatin showed promising antitumor activity in advanced biliary tract cancer. This latest study is a larger phase 3 trial to investigate this effect further.

The study involved 365 patients with unresectable locally advanced, recurrent, or metastatic biliary tract cancers. Patients had one of three types of biliary tract cancer: 55% had intrahepatic cancers; 19% had extrahepatic cancers; and 25% had gallbladder cancer.

The trial was conducted in the U.S. and 17 countries in Europe, South America, and Asia. Nearly 55% of the cohort was from Asia, including South Korea, Thailand, Japan, and China.

All patients received chemotherapy with gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m² on days 1 and 8 every 3 weeks) for up to eight cycles.

Patients were randomized to receive either durvalumab (1,500 mg every 3 weeks) or placebo before chemotherapy and also to receive durvalumab (1,500 mg every 4 weeks) or placebo after chemotherapy until disease progression or unacceptable toxicity.

At approximately 1 year, the authors found that adding durvalumab significantly improved overall survival (hazard ratio, 0.80; P = .021).

Progression-free survival was also significantly better with durvalumab compared to placebo: 7.2 months versus 5.7 months (HR, 0.75; P = .001).

The overall response rate (ORR) was 26.7% with durvalumab and 18.7% with placebo.

The most common adverse events were anemia (experienced by 48.2% of patients), neutropenia (31.7%), and nausea (40.2%). Grade 3/4 adverse events occurred in 75.7% of patients receiving durvalumab versus 77.8% for placebo, indicating that the majority of side effects in both arms were from chemotherapy, Dr. Oh commented. Discontinuation of any study medication because of toxicity occurred in 8.9% and 11.4% of patients, respectively.
 

Enticing benefit, but questions remain

In her discussion of the paper, Dr. Azad pointed out that Asian patients comprised more than half of the cohort and appeared to derive more benefit from the investigational treatment compared to other groups. “So the question is if that is driving the benefit or just an increased benefit,” she said. “That is going to be an open question for our research community.”

Dr. Azad also noted that patients with nonmetastatic disease at enrollment did a little better, so more data are needed on how that affected the outcomes.

“PDL-1 just missed statistical significance, but that is something that will be further explored,” she said. “And we still have open questions about viral hepatitis, liver fluke infection, and cirrhosis, and I do hope that these will be included in the final analysis of the study.”

The GICS meeting is organized by the American Society of Clinical Oncology (ASCO), and the society highlighted these data in a press release. Cathy Eng, MD, FACP, ASCO expert in gastrointestinal cancers, commented in the statement: “TOPAZ-1 is the first phase 3 trial to demonstrate the benefit of immunotherapy for improved overall survival, in combination with chemotherapy, creating a new standard of care.”

The study received funding from AstraZeneca, marker of durvalumab. Dr. Oh and Dr. Azad reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Adding the checkpoint inhibitor durvalumab (Imfinzi) to chemotherapy significantly improved overall survival in patients with advanced biliary tract cancer, as compared to chemotherapy alone, according to interim results from the TOPAZ-1 trial.

The risk of death for those taking durvalumab plus chemotherapy was 20% lower than for patients on chemotherapy alone. At 18 months, overall survival was 35.1% in the durvalumab group versus 25.6% for chemotherapy alone. By 2 years, overall survival was 24.9% versus 10.4%.

“TOPAZ-1 is the first phase 3 trial to show that adding immunotherapy to standard chemotherapy can increase survival in biliary tract cancer, and importantly, does so without inducing any new serious side effects,” said lead author Do-Youn Oh, MD, PhD, professor in the Division of Medical Oncology at Seoul National University Hospital and Seoul National University College of Medicine, Korea.

“The study met its primary endpoint at a prespecified interim analysis, and durvalumab plus gemcitabine and cisplatin demonstrated statistically significant and clinically meaningful prolonged overall survival compared with placebo plus chemotherapy,” she said.

“This is an effective first-line therapy and could become a new standard of care for patients with advanced biliary tract cancer,” she added.

Dr. Oh presented the results at the Gastrointestinal Cancers Symposium (GICS) 2022.

In a discussion of the paper, Nilofer Saba Azad, MD, from the department of oncology, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, noted that overall, “we are seeing enticing benefit in survival and response rate.”

“There is moderately strong preliminary clinical data and biological rationale that immune checkpoint may have some activity in biliary tract cancer,” she said. “The trial was adequately powered and accounted for important known clinical subsets, and [it] was placebo controlled. The results suggest a meaningful benefit for patients.”

However, she pointed out that there are still open questions, mostly having to do with the subgroup analysis.
 

Biliary tract cancer: Incidence is rising

Biliary tract cancers are a relatively rare and heterogeneous group of cancers, and global incidence is rising. “Advanced unresectable biliary tract cancer is an area of high unmet need due to its aggressive nature, limited treatment options, and poor prognosis,” explained Dr. Oh. “The first-line standard of care for advanced biliary tract cancers, gemcitabine and cisplatin, has remained unchanged for over a decade.”

Previous research has suggested that checkpoint inhibition may result in antitumor immune responses, she commented. A previous phase 2 trial showed that durvalumab combined with gemcitabine and cisplatin showed promising antitumor activity in advanced biliary tract cancer. This latest study is a larger phase 3 trial to investigate this effect further.

The study involved 365 patients with unresectable locally advanced, recurrent, or metastatic biliary tract cancers. Patients had one of three types of biliary tract cancer: 55% had intrahepatic cancers; 19% had extrahepatic cancers; and 25% had gallbladder cancer.

The trial was conducted in the U.S. and 17 countries in Europe, South America, and Asia. Nearly 55% of the cohort was from Asia, including South Korea, Thailand, Japan, and China.

All patients received chemotherapy with gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m² on days 1 and 8 every 3 weeks) for up to eight cycles.

Patients were randomized to receive either durvalumab (1,500 mg every 3 weeks) or placebo before chemotherapy and also to receive durvalumab (1,500 mg every 4 weeks) or placebo after chemotherapy until disease progression or unacceptable toxicity.

At approximately 1 year, the authors found that adding durvalumab significantly improved overall survival (hazard ratio, 0.80; P = .021).

Progression-free survival was also significantly better with durvalumab compared to placebo: 7.2 months versus 5.7 months (HR, 0.75; P = .001).

The overall response rate (ORR) was 26.7% with durvalumab and 18.7% with placebo.

The most common adverse events were anemia (experienced by 48.2% of patients), neutropenia (31.7%), and nausea (40.2%). Grade 3/4 adverse events occurred in 75.7% of patients receiving durvalumab versus 77.8% for placebo, indicating that the majority of side effects in both arms were from chemotherapy, Dr. Oh commented. Discontinuation of any study medication because of toxicity occurred in 8.9% and 11.4% of patients, respectively.
 

Enticing benefit, but questions remain

In her discussion of the paper, Dr. Azad pointed out that Asian patients comprised more than half of the cohort and appeared to derive more benefit from the investigational treatment compared to other groups. “So the question is if that is driving the benefit or just an increased benefit,” she said. “That is going to be an open question for our research community.”

Dr. Azad also noted that patients with nonmetastatic disease at enrollment did a little better, so more data are needed on how that affected the outcomes.

“PDL-1 just missed statistical significance, but that is something that will be further explored,” she said. “And we still have open questions about viral hepatitis, liver fluke infection, and cirrhosis, and I do hope that these will be included in the final analysis of the study.”

The GICS meeting is organized by the American Society of Clinical Oncology (ASCO), and the society highlighted these data in a press release. Cathy Eng, MD, FACP, ASCO expert in gastrointestinal cancers, commented in the statement: “TOPAZ-1 is the first phase 3 trial to demonstrate the benefit of immunotherapy for improved overall survival, in combination with chemotherapy, creating a new standard of care.”

The study received funding from AstraZeneca, marker of durvalumab. Dr. Oh and Dr. Azad reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Adding the checkpoint inhibitor durvalumab (Imfinzi) to chemotherapy significantly improved overall survival in patients with advanced biliary tract cancer, as compared to chemotherapy alone, according to interim results from the TOPAZ-1 trial.

The risk of death for those taking durvalumab plus chemotherapy was 20% lower than for patients on chemotherapy alone. At 18 months, overall survival was 35.1% in the durvalumab group versus 25.6% for chemotherapy alone. By 2 years, overall survival was 24.9% versus 10.4%.

“TOPAZ-1 is the first phase 3 trial to show that adding immunotherapy to standard chemotherapy can increase survival in biliary tract cancer, and importantly, does so without inducing any new serious side effects,” said lead author Do-Youn Oh, MD, PhD, professor in the Division of Medical Oncology at Seoul National University Hospital and Seoul National University College of Medicine, Korea.

“The study met its primary endpoint at a prespecified interim analysis, and durvalumab plus gemcitabine and cisplatin demonstrated statistically significant and clinically meaningful prolonged overall survival compared with placebo plus chemotherapy,” she said.

“This is an effective first-line therapy and could become a new standard of care for patients with advanced biliary tract cancer,” she added.

Dr. Oh presented the results at the Gastrointestinal Cancers Symposium (GICS) 2022.

In a discussion of the paper, Nilofer Saba Azad, MD, from the department of oncology, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, noted that overall, “we are seeing enticing benefit in survival and response rate.”

“There is moderately strong preliminary clinical data and biological rationale that immune checkpoint may have some activity in biliary tract cancer,” she said. “The trial was adequately powered and accounted for important known clinical subsets, and [it] was placebo controlled. The results suggest a meaningful benefit for patients.”

However, she pointed out that there are still open questions, mostly having to do with the subgroup analysis.
 

Biliary tract cancer: Incidence is rising

Biliary tract cancers are a relatively rare and heterogeneous group of cancers, and global incidence is rising. “Advanced unresectable biliary tract cancer is an area of high unmet need due to its aggressive nature, limited treatment options, and poor prognosis,” explained Dr. Oh. “The first-line standard of care for advanced biliary tract cancers, gemcitabine and cisplatin, has remained unchanged for over a decade.”

Previous research has suggested that checkpoint inhibition may result in antitumor immune responses, she commented. A previous phase 2 trial showed that durvalumab combined with gemcitabine and cisplatin showed promising antitumor activity in advanced biliary tract cancer. This latest study is a larger phase 3 trial to investigate this effect further.

The study involved 365 patients with unresectable locally advanced, recurrent, or metastatic biliary tract cancers. Patients had one of three types of biliary tract cancer: 55% had intrahepatic cancers; 19% had extrahepatic cancers; and 25% had gallbladder cancer.

The trial was conducted in the U.S. and 17 countries in Europe, South America, and Asia. Nearly 55% of the cohort was from Asia, including South Korea, Thailand, Japan, and China.

All patients received chemotherapy with gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m² on days 1 and 8 every 3 weeks) for up to eight cycles.

Patients were randomized to receive either durvalumab (1,500 mg every 3 weeks) or placebo before chemotherapy and also to receive durvalumab (1,500 mg every 4 weeks) or placebo after chemotherapy until disease progression or unacceptable toxicity.

At approximately 1 year, the authors found that adding durvalumab significantly improved overall survival (hazard ratio, 0.80; P = .021).

Progression-free survival was also significantly better with durvalumab compared to placebo: 7.2 months versus 5.7 months (HR, 0.75; P = .001).

The overall response rate (ORR) was 26.7% with durvalumab and 18.7% with placebo.

The most common adverse events were anemia (experienced by 48.2% of patients), neutropenia (31.7%), and nausea (40.2%). Grade 3/4 adverse events occurred in 75.7% of patients receiving durvalumab versus 77.8% for placebo, indicating that the majority of side effects in both arms were from chemotherapy, Dr. Oh commented. Discontinuation of any study medication because of toxicity occurred in 8.9% and 11.4% of patients, respectively.
 

Enticing benefit, but questions remain

In her discussion of the paper, Dr. Azad pointed out that Asian patients comprised more than half of the cohort and appeared to derive more benefit from the investigational treatment compared to other groups. “So the question is if that is driving the benefit or just an increased benefit,” she said. “That is going to be an open question for our research community.”

Dr. Azad also noted that patients with nonmetastatic disease at enrollment did a little better, so more data are needed on how that affected the outcomes.

“PDL-1 just missed statistical significance, but that is something that will be further explored,” she said. “And we still have open questions about viral hepatitis, liver fluke infection, and cirrhosis, and I do hope that these will be included in the final analysis of the study.”

The GICS meeting is organized by the American Society of Clinical Oncology (ASCO), and the society highlighted these data in a press release. Cathy Eng, MD, FACP, ASCO expert in gastrointestinal cancers, commented in the statement: “TOPAZ-1 is the first phase 3 trial to demonstrate the benefit of immunotherapy for improved overall survival, in combination with chemotherapy, creating a new standard of care.”

The study received funding from AstraZeneca, marker of durvalumab. Dr. Oh and Dr. Azad reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Vitamin D supplementation did not appear to influence the incidence of cancer or major cardiovascular disease (CVD) events in older adults who largely already had adequate vitamin D levels, according to a new randomized controlled study.

In the cohort of nearly 2,500 healthy individuals, the researchers found no differences in cancer or CVD incidence over 5 years between the groups randomly assigned to vitamin D supplementation and to placebo.

The findings, published online Jan. 4, 2022, in the American Journal of Clinical Nutrition, may be influenced by the fact that most participants had sufficient vitamin D levels at baseline, and thus received higher than recommended doses of vitamin D during the study.

“Vitamin D₃ supplementation with 1600 or 3200 IU/day for 5 years did not reduce the incidence of major CVD events, any invasive cancer, or mortality among generally healthy and mostly vitamin D sufficient older adults in Finland,” write the authors, led by Jyrki Virtanen, RD, PhD, associate professor of nutrition and public health at University of Eastern Finland, Kuopio.

“The low number of subjects with low vitamin D concentrations was a bit of a surprise for us also, but it likely reflects the quite successful food fortification policy in Finland,” Dr. Virtanen told this news organization.

Prior research has found that vitamin D insufficiency is associated with a higher risk of nearly all diseases. Although the evidence on the benefits of vitamin D supplementation remains more limited, a meta-analysis reported a consistent and significant 13% reduction in cancer mortality in those who received vitamin D supplements.

In this study, Dr. Virtanen and colleagues investigated the effects of vitamin D₃ supplementation on cancer and CVD incidence in a cohort of 2,495 healthy participants.

Men 60 years or older and women 65 years or older were randomly assigned to one of three groups: placebo, 40 mcg (1,600 IU) of daily vitamin D₃, or 80 mcg (3,200 IU) of daily vitamin D₃.

Data collected at baseline and throughout the trial included serum 25(OH)D concentrations, nutrition, sun exposure, medication use, mental health, and other factors that could affect the risk of disease.

The study’s primary endpoints were incident of major CVD and invasive cancer. Secondary endpoints included incidence of myocardial infarction, stroke, and CVD mortality as well as site-specific cancers and cancer death.

Follow-up occurred via annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person evaluations. In the sub-cohort, mean serum 25(OH)D concentration was 75 nmol/L (30 ng/mL) at baseline; 9.1% had concentrations less than 50 nmol/L (20 ng/mL) and 50.0% had concentrations of at least 75 nmol/L (30 ng/mL).

The authors identified no major differences between the three arms at baseline, but noted that, compared with the overall study population, those in the subcohort were younger, more likely to use their own vitamin D supplements, and more likely to rate their health as good or excellent.

Among 503 participants that had complete data from baseline, the mean increase in serum 25(OH)D in participants receiving 1,600 IU/day vitamin D₃ was 23.4 nmol/L (9.4 ng/mL) and 43.6 nmol/L (17.4 ng/mL) in the arm receiving 3,200 IU/day between baseline and 6 months. The authors observed a small additional increase in levels between the 6-month and 12-month visits, but few changes in vitamin D₃ levels in the placebo arm.

At the 5-year follow-up, major CVD events occurred in 4.9% of participants in the placebo arm, 5% in those in the 1,600 IU/d arm (hazard ratio, 0.97), and 4.3% of those in the 3,200 IU/d arm (HR, 0.84; P = .44). Invasive cancer at follow-up was diagnosed in 4.9% of placebo recipients, 5.8% of those on 1,600 IU/d supplementation (HR, 1.14; P = .55), and 4.8% in the 3,200 IU/d group (HR, 0.95; P = .81). No significant differences were observed in the secondary endpoints or in total mortality.

The authors did not conduct a subanalysis in participants who had low 25(OH)D concentrations levels at baseline because “there were too few participants to do any meaningful analyses,” said Dr. Virtanen, who noted that blood samples were available for a representative subgroup of 550 subjects, and only 9% of them had low 25(OH)D concentrations at baseline.

Dr. Virtanen noted that future vitamin D supplementation trials should focus on recruiting participants with low vitamin D status.

The study was supported by funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, Medicinska Understödsföreningen Liv och Hälsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, and Finnish Cultural Foundation. Dr. Virtanen disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vitamin D supplementation did not appear to influence the incidence of cancer or major cardiovascular disease (CVD) events in older adults who largely already had adequate vitamin D levels, according to a new randomized controlled study.

In the cohort of nearly 2,500 healthy individuals, the researchers found no differences in cancer or CVD incidence over 5 years between the groups randomly assigned to vitamin D supplementation and to placebo.

The findings, published online Jan. 4, 2022, in the American Journal of Clinical Nutrition, may be influenced by the fact that most participants had sufficient vitamin D levels at baseline, and thus received higher than recommended doses of vitamin D during the study.

“Vitamin D₃ supplementation with 1600 or 3200 IU/day for 5 years did not reduce the incidence of major CVD events, any invasive cancer, or mortality among generally healthy and mostly vitamin D sufficient older adults in Finland,” write the authors, led by Jyrki Virtanen, RD, PhD, associate professor of nutrition and public health at University of Eastern Finland, Kuopio.

“The low number of subjects with low vitamin D concentrations was a bit of a surprise for us also, but it likely reflects the quite successful food fortification policy in Finland,” Dr. Virtanen told this news organization.

Prior research has found that vitamin D insufficiency is associated with a higher risk of nearly all diseases. Although the evidence on the benefits of vitamin D supplementation remains more limited, a meta-analysis reported a consistent and significant 13% reduction in cancer mortality in those who received vitamin D supplements.

In this study, Dr. Virtanen and colleagues investigated the effects of vitamin D₃ supplementation on cancer and CVD incidence in a cohort of 2,495 healthy participants.

Men 60 years or older and women 65 years or older were randomly assigned to one of three groups: placebo, 40 mcg (1,600 IU) of daily vitamin D₃, or 80 mcg (3,200 IU) of daily vitamin D₃.

Data collected at baseline and throughout the trial included serum 25(OH)D concentrations, nutrition, sun exposure, medication use, mental health, and other factors that could affect the risk of disease.

The study’s primary endpoints were incident of major CVD and invasive cancer. Secondary endpoints included incidence of myocardial infarction, stroke, and CVD mortality as well as site-specific cancers and cancer death.

Follow-up occurred via annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person evaluations. In the sub-cohort, mean serum 25(OH)D concentration was 75 nmol/L (30 ng/mL) at baseline; 9.1% had concentrations less than 50 nmol/L (20 ng/mL) and 50.0% had concentrations of at least 75 nmol/L (30 ng/mL).

The authors identified no major differences between the three arms at baseline, but noted that, compared with the overall study population, those in the subcohort were younger, more likely to use their own vitamin D supplements, and more likely to rate their health as good or excellent.

Among 503 participants that had complete data from baseline, the mean increase in serum 25(OH)D in participants receiving 1,600 IU/day vitamin D₃ was 23.4 nmol/L (9.4 ng/mL) and 43.6 nmol/L (17.4 ng/mL) in the arm receiving 3,200 IU/day between baseline and 6 months. The authors observed a small additional increase in levels between the 6-month and 12-month visits, but few changes in vitamin D₃ levels in the placebo arm.

At the 5-year follow-up, major CVD events occurred in 4.9% of participants in the placebo arm, 5% in those in the 1,600 IU/d arm (hazard ratio, 0.97), and 4.3% of those in the 3,200 IU/d arm (HR, 0.84; P = .44). Invasive cancer at follow-up was diagnosed in 4.9% of placebo recipients, 5.8% of those on 1,600 IU/d supplementation (HR, 1.14; P = .55), and 4.8% in the 3,200 IU/d group (HR, 0.95; P = .81). No significant differences were observed in the secondary endpoints or in total mortality.

The authors did not conduct a subanalysis in participants who had low 25(OH)D concentrations levels at baseline because “there were too few participants to do any meaningful analyses,” said Dr. Virtanen, who noted that blood samples were available for a representative subgroup of 550 subjects, and only 9% of them had low 25(OH)D concentrations at baseline.

Dr. Virtanen noted that future vitamin D supplementation trials should focus on recruiting participants with low vitamin D status.

The study was supported by funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, Medicinska Understödsföreningen Liv och Hälsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, and Finnish Cultural Foundation. Dr. Virtanen disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vitamin D supplementation did not appear to influence the incidence of cancer or major cardiovascular disease (CVD) events in older adults who largely already had adequate vitamin D levels, according to a new randomized controlled study.

In the cohort of nearly 2,500 healthy individuals, the researchers found no differences in cancer or CVD incidence over 5 years between the groups randomly assigned to vitamin D supplementation and to placebo.

The findings, published online Jan. 4, 2022, in the American Journal of Clinical Nutrition, may be influenced by the fact that most participants had sufficient vitamin D levels at baseline, and thus received higher than recommended doses of vitamin D during the study.

“Vitamin D₃ supplementation with 1600 or 3200 IU/day for 5 years did not reduce the incidence of major CVD events, any invasive cancer, or mortality among generally healthy and mostly vitamin D sufficient older adults in Finland,” write the authors, led by Jyrki Virtanen, RD, PhD, associate professor of nutrition and public health at University of Eastern Finland, Kuopio.

“The low number of subjects with low vitamin D concentrations was a bit of a surprise for us also, but it likely reflects the quite successful food fortification policy in Finland,” Dr. Virtanen told this news organization.

Prior research has found that vitamin D insufficiency is associated with a higher risk of nearly all diseases. Although the evidence on the benefits of vitamin D supplementation remains more limited, a meta-analysis reported a consistent and significant 13% reduction in cancer mortality in those who received vitamin D supplements.

In this study, Dr. Virtanen and colleagues investigated the effects of vitamin D₃ supplementation on cancer and CVD incidence in a cohort of 2,495 healthy participants.

Men 60 years or older and women 65 years or older were randomly assigned to one of three groups: placebo, 40 mcg (1,600 IU) of daily vitamin D₃, or 80 mcg (3,200 IU) of daily vitamin D₃.

Data collected at baseline and throughout the trial included serum 25(OH)D concentrations, nutrition, sun exposure, medication use, mental health, and other factors that could affect the risk of disease.

The study’s primary endpoints were incident of major CVD and invasive cancer. Secondary endpoints included incidence of myocardial infarction, stroke, and CVD mortality as well as site-specific cancers and cancer death.

Follow-up occurred via annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person evaluations. In the sub-cohort, mean serum 25(OH)D concentration was 75 nmol/L (30 ng/mL) at baseline; 9.1% had concentrations less than 50 nmol/L (20 ng/mL) and 50.0% had concentrations of at least 75 nmol/L (30 ng/mL).

The authors identified no major differences between the three arms at baseline, but noted that, compared with the overall study population, those in the subcohort were younger, more likely to use their own vitamin D supplements, and more likely to rate their health as good or excellent.

Among 503 participants that had complete data from baseline, the mean increase in serum 25(OH)D in participants receiving 1,600 IU/day vitamin D₃ was 23.4 nmol/L (9.4 ng/mL) and 43.6 nmol/L (17.4 ng/mL) in the arm receiving 3,200 IU/day between baseline and 6 months. The authors observed a small additional increase in levels between the 6-month and 12-month visits, but few changes in vitamin D₃ levels in the placebo arm.

At the 5-year follow-up, major CVD events occurred in 4.9% of participants in the placebo arm, 5% in those in the 1,600 IU/d arm (hazard ratio, 0.97), and 4.3% of those in the 3,200 IU/d arm (HR, 0.84; P = .44). Invasive cancer at follow-up was diagnosed in 4.9% of placebo recipients, 5.8% of those on 1,600 IU/d supplementation (HR, 1.14; P = .55), and 4.8% in the 3,200 IU/d group (HR, 0.95; P = .81). No significant differences were observed in the secondary endpoints or in total mortality.

The authors did not conduct a subanalysis in participants who had low 25(OH)D concentrations levels at baseline because “there were too few participants to do any meaningful analyses,” said Dr. Virtanen, who noted that blood samples were available for a representative subgroup of 550 subjects, and only 9% of them had low 25(OH)D concentrations at baseline.

Dr. Virtanen noted that future vitamin D supplementation trials should focus on recruiting participants with low vitamin D status.

The study was supported by funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, Medicinska Understödsföreningen Liv och Hälsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, and Finnish Cultural Foundation. Dr. Virtanen disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.