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Treating bone loss ups survival for breast cancer patients
A final long-term analysis of a study designed to evaluate the safety of a common osteoporosis drug used to treat bone loss in women who were treated for breast cancer, finds the
The final analysis of “Adjuvant Denosumab in Breast Cancer (ABCSG-18)” was presented at the annual meeting of the American Society of Clinical Oncology.
“Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer on aromatase inhibitors treatment,” said the study’s author Michael Gnant, MD, FACS, director of surgery for the Medical University of Vienna.
Denosumab is currently recommended by ASCO as a treatment option for osteoporosis in patients who were successfully treated for nonmetastatic disease.
ABCSG-18 was a prospective, double-blind, placebo-controlled, phase 3 trial that comprised 3,420 patients (mean age 64.5 years) from 58 treatment centers. It included postmenopausal patients with early HR+ breast cancer who were treated with aromatase inhibitors between 2006 and 2013. Among the patients, 1,711 received denosumab 60 mg and 1,709 received a placebo every 6 months.
The primary endpoint was time to first clinical fracture, and the secondary disease outcome-related endpoints were disease-free survival, bone metastasis–free survival, and overall survival.
The hazard ratio for disease-free survival in the denosumab group was 0.83 (95% confidence interval [CI], 0.71-0.97, P = .02) after a median follow-up of 8 years. Disease-free survival (DFS) was 69.0% in the placebo arm and 74.4% in the denosumab arm, with events occurring in 19.8% of patients overall, including deaths in 8.3%.
Bone metastasis–free survival (BMFS) rates were 81.3% and 85.7% in the placebo and denosumab arms, respectively (HR = 0.81, 95% CI, 0.65-1.00, P = .05). Overall survival was 83.6% and 88.8% in the placebo and denosumab arms, respectively (HR = 0.80; 95% CI, 0.63-1.01, P = .06).
There were no new toxicities, nor was there a single positive case of osteonecrosis of the jaw (ONJ) during the study period, which may be due to the low dosage of denosumab. The bone protection dose of denosumab is much lower than that used for treatment of metastases which can be 12 times higher. In those cases, 4%-6% of patients may develop ONJ. “At these very low doses, even after 30,000 treatment years, we did not observe a single confirmed ONJ case,” he said.
Exploratory observations showed the majority of events to include distant recurrences in bone, liver, and lungs. Analysis revealed a trend toward reduction in contralateral breast cancer in the denosumab arm (24 versus 29 events), with a reduction in second non-breast primary malignancies (101 versus 127 events).
In a much earlier ABCSG-18 study from 2015, the primary endpoint of fracture risk was reduced significantly with denosumab (HR = 0.50, P < .0001), with highly significantly longer time to first clinical fracture, higher percent increase in bone mineral density (P < .0001 for both) and fewer vertebral fractures (P = .009). There is evidence that older generation bisphosphonates have potential beyond bone health, such as reducing metabolism (which benefits bone turnover), and improving breast cancer outcomes. These benefits sparked interest in potential long-term cancer reduction with denosumab, Dr. Gnant said.
“Bone marrow is a putative source of late relapse. Tumor cells can harbor there in a quiescent state for 10-15-20 years, and then for some reason wake up and cause metastases. So, all bone-targeted agents are also evaluated for reductions in cancer which is what we were looking to investigate here in this 15-year data,” he said. Denosumab is more targeted than the bisphosphonates, and directly inhibits the RANK ligand which is an important mediator of osteoclast activation. “This ligand is believed to support metastases in the process of waking up,” Dr. Gnant said.
A limitation of the study is that the outcome endpoints of ABCSG-18 are secondary ones, making the results technically descriptive. The study was sponsored by Amgen.
A final long-term analysis of a study designed to evaluate the safety of a common osteoporosis drug used to treat bone loss in women who were treated for breast cancer, finds the
The final analysis of “Adjuvant Denosumab in Breast Cancer (ABCSG-18)” was presented at the annual meeting of the American Society of Clinical Oncology.
“Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer on aromatase inhibitors treatment,” said the study’s author Michael Gnant, MD, FACS, director of surgery for the Medical University of Vienna.
Denosumab is currently recommended by ASCO as a treatment option for osteoporosis in patients who were successfully treated for nonmetastatic disease.
ABCSG-18 was a prospective, double-blind, placebo-controlled, phase 3 trial that comprised 3,420 patients (mean age 64.5 years) from 58 treatment centers. It included postmenopausal patients with early HR+ breast cancer who were treated with aromatase inhibitors between 2006 and 2013. Among the patients, 1,711 received denosumab 60 mg and 1,709 received a placebo every 6 months.
The primary endpoint was time to first clinical fracture, and the secondary disease outcome-related endpoints were disease-free survival, bone metastasis–free survival, and overall survival.
The hazard ratio for disease-free survival in the denosumab group was 0.83 (95% confidence interval [CI], 0.71-0.97, P = .02) after a median follow-up of 8 years. Disease-free survival (DFS) was 69.0% in the placebo arm and 74.4% in the denosumab arm, with events occurring in 19.8% of patients overall, including deaths in 8.3%.
Bone metastasis–free survival (BMFS) rates were 81.3% and 85.7% in the placebo and denosumab arms, respectively (HR = 0.81, 95% CI, 0.65-1.00, P = .05). Overall survival was 83.6% and 88.8% in the placebo and denosumab arms, respectively (HR = 0.80; 95% CI, 0.63-1.01, P = .06).
There were no new toxicities, nor was there a single positive case of osteonecrosis of the jaw (ONJ) during the study period, which may be due to the low dosage of denosumab. The bone protection dose of denosumab is much lower than that used for treatment of metastases which can be 12 times higher. In those cases, 4%-6% of patients may develop ONJ. “At these very low doses, even after 30,000 treatment years, we did not observe a single confirmed ONJ case,” he said.
Exploratory observations showed the majority of events to include distant recurrences in bone, liver, and lungs. Analysis revealed a trend toward reduction in contralateral breast cancer in the denosumab arm (24 versus 29 events), with a reduction in second non-breast primary malignancies (101 versus 127 events).
In a much earlier ABCSG-18 study from 2015, the primary endpoint of fracture risk was reduced significantly with denosumab (HR = 0.50, P < .0001), with highly significantly longer time to first clinical fracture, higher percent increase in bone mineral density (P < .0001 for both) and fewer vertebral fractures (P = .009). There is evidence that older generation bisphosphonates have potential beyond bone health, such as reducing metabolism (which benefits bone turnover), and improving breast cancer outcomes. These benefits sparked interest in potential long-term cancer reduction with denosumab, Dr. Gnant said.
“Bone marrow is a putative source of late relapse. Tumor cells can harbor there in a quiescent state for 10-15-20 years, and then for some reason wake up and cause metastases. So, all bone-targeted agents are also evaluated for reductions in cancer which is what we were looking to investigate here in this 15-year data,” he said. Denosumab is more targeted than the bisphosphonates, and directly inhibits the RANK ligand which is an important mediator of osteoclast activation. “This ligand is believed to support metastases in the process of waking up,” Dr. Gnant said.
A limitation of the study is that the outcome endpoints of ABCSG-18 are secondary ones, making the results technically descriptive. The study was sponsored by Amgen.
A final long-term analysis of a study designed to evaluate the safety of a common osteoporosis drug used to treat bone loss in women who were treated for breast cancer, finds the
The final analysis of “Adjuvant Denosumab in Breast Cancer (ABCSG-18)” was presented at the annual meeting of the American Society of Clinical Oncology.
“Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer on aromatase inhibitors treatment,” said the study’s author Michael Gnant, MD, FACS, director of surgery for the Medical University of Vienna.
Denosumab is currently recommended by ASCO as a treatment option for osteoporosis in patients who were successfully treated for nonmetastatic disease.
ABCSG-18 was a prospective, double-blind, placebo-controlled, phase 3 trial that comprised 3,420 patients (mean age 64.5 years) from 58 treatment centers. It included postmenopausal patients with early HR+ breast cancer who were treated with aromatase inhibitors between 2006 and 2013. Among the patients, 1,711 received denosumab 60 mg and 1,709 received a placebo every 6 months.
The primary endpoint was time to first clinical fracture, and the secondary disease outcome-related endpoints were disease-free survival, bone metastasis–free survival, and overall survival.
The hazard ratio for disease-free survival in the denosumab group was 0.83 (95% confidence interval [CI], 0.71-0.97, P = .02) after a median follow-up of 8 years. Disease-free survival (DFS) was 69.0% in the placebo arm and 74.4% in the denosumab arm, with events occurring in 19.8% of patients overall, including deaths in 8.3%.
Bone metastasis–free survival (BMFS) rates were 81.3% and 85.7% in the placebo and denosumab arms, respectively (HR = 0.81, 95% CI, 0.65-1.00, P = .05). Overall survival was 83.6% and 88.8% in the placebo and denosumab arms, respectively (HR = 0.80; 95% CI, 0.63-1.01, P = .06).
There were no new toxicities, nor was there a single positive case of osteonecrosis of the jaw (ONJ) during the study period, which may be due to the low dosage of denosumab. The bone protection dose of denosumab is much lower than that used for treatment of metastases which can be 12 times higher. In those cases, 4%-6% of patients may develop ONJ. “At these very low doses, even after 30,000 treatment years, we did not observe a single confirmed ONJ case,” he said.
Exploratory observations showed the majority of events to include distant recurrences in bone, liver, and lungs. Analysis revealed a trend toward reduction in contralateral breast cancer in the denosumab arm (24 versus 29 events), with a reduction in second non-breast primary malignancies (101 versus 127 events).
In a much earlier ABCSG-18 study from 2015, the primary endpoint of fracture risk was reduced significantly with denosumab (HR = 0.50, P < .0001), with highly significantly longer time to first clinical fracture, higher percent increase in bone mineral density (P < .0001 for both) and fewer vertebral fractures (P = .009). There is evidence that older generation bisphosphonates have potential beyond bone health, such as reducing metabolism (which benefits bone turnover), and improving breast cancer outcomes. These benefits sparked interest in potential long-term cancer reduction with denosumab, Dr. Gnant said.
“Bone marrow is a putative source of late relapse. Tumor cells can harbor there in a quiescent state for 10-15-20 years, and then for some reason wake up and cause metastases. So, all bone-targeted agents are also evaluated for reductions in cancer which is what we were looking to investigate here in this 15-year data,” he said. Denosumab is more targeted than the bisphosphonates, and directly inhibits the RANK ligand which is an important mediator of osteoclast activation. “This ligand is believed to support metastases in the process of waking up,” Dr. Gnant said.
A limitation of the study is that the outcome endpoints of ABCSG-18 are secondary ones, making the results technically descriptive. The study was sponsored by Amgen.
FROM ASCO 2022
Pembrolizumab before surgery improves survival in early triple negative breast cancer
for improving survival in patients with early triple negative breast cancer (TNBC).
The findings were presented in Chicago June 4 and 5 at the annual meeting of the American Society of Clinical Oncology by study author Lajos Pusztai, MD, D.Phil, director of Breast Cancer Translational Research at Yale University, New Haven, Conn.
KEYNOTE-522 is the first prospective, randomized, placebo-controlled phase 3 trial of pembrolizumab for early-stage TNBC in the neoadjuvant and adjuvant setting.
The study included 1,174 patients (median age 49 years) with previously untreated stage II or III triple-negative breast cancer. Patients were randomly assigned to receive neoadjuvant therapy with four cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After surgery, patients received pembrolizumab or placebeo for 9 cycles or until recurrence or unacceptable toxicity. The primary end points were pathological complete response and event-free survival.
A total of 784 patients were treated with pembrolizumab and chemotherapy, and the second group of 390 patients received a placebo and chemotherapy. After surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo and chemotherapy for every 3 weeks for up to nine cycles.
The estimated event-free survival at 36 months was 84.5% in the pembrolizumab-chemotherapy group, compared with 76.8% in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% confidence interval, 0.48 to 0.82; P <0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.
At the first interim analysis, 64.8% achieved pathological complete response in the pembrolizumab group versus 51.2% in the placebo group. At the fourth interim analysis at 36 months, event-free survival was 76.8% in the placebo arm and 84.5% in the pembrolizumab arm. RCB-0 status was achieved by 63.4% and 56.2% of patients in the pembrolizumab and placebo arms, respectively.
Pembrolizumab did contribute immune-related adverse events, mostly grades 1-2, in about 17% of patients with thyroid function abnormalities most common with most occurring 20 weeks prior to surgical treatment.
Treatment with pembrolizumab added to chemotherapy, compared with chemotherapy alone, shifted residual cancer burden to lower categories across the entire spectrum of patients in the trial.
The hazard ratio for event-free survival with RCB-0, which Dr. Pusztai said is equivalent to a pathologic complete response (pCR), was 0.70 (0.38-1.31). For RCB-1 (minimal residual disease) it was 0.92 (0.39-2.20); for RCB-2 (moderate residual disease) it was 0.52 (0.32-0.82); and for RCB-3 (extensive residual disease) it was 1.24 (0.69-2.23).
“The most important finding is that patients in RCB-2, a group with a moderate amount of residual disease, experienced significant improvement with pembrolizumab. This clearly indicates not only that pembrolizumab leads to higher pCR rates but also that the pembrolizumCR/RCB-0 ... extends to patients who do not achieve pCR,” Dr. Pusztai said.
The benefit, he suggested, could be a result of the adjuvant pembrolizumab maintenance phase.
Patients in the RCB-3 category do poorly regardless of treatment (EFS of 34.6 % and 26.2% in the pembrolizumab and placebo arms, respectively).
“The RCB-3 population represents an unmet medical need, and they will need better drugs, and additional postoperative adjuvant therapy,” Dr. Pusztai said. The current standard of care is capecitabine for 6-8 cycles. Emerging new therapies, such as antibody drug conjugates, will be tested, he said.
In terms of limitations, adjuvant capecitabine was not allowed. “It remains uncertain how much better the RCB-2 and -3 patient outcomes would have been if capecitabine were administered,” he said.
The study was funded by Merck Sharp and Dohme, a subsidiary of Merck. Dr. Pusztai has received consulting fees and honoraria from Merck.
for improving survival in patients with early triple negative breast cancer (TNBC).
The findings were presented in Chicago June 4 and 5 at the annual meeting of the American Society of Clinical Oncology by study author Lajos Pusztai, MD, D.Phil, director of Breast Cancer Translational Research at Yale University, New Haven, Conn.
KEYNOTE-522 is the first prospective, randomized, placebo-controlled phase 3 trial of pembrolizumab for early-stage TNBC in the neoadjuvant and adjuvant setting.
The study included 1,174 patients (median age 49 years) with previously untreated stage II or III triple-negative breast cancer. Patients were randomly assigned to receive neoadjuvant therapy with four cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After surgery, patients received pembrolizumab or placebeo for 9 cycles or until recurrence or unacceptable toxicity. The primary end points were pathological complete response and event-free survival.
A total of 784 patients were treated with pembrolizumab and chemotherapy, and the second group of 390 patients received a placebo and chemotherapy. After surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo and chemotherapy for every 3 weeks for up to nine cycles.
The estimated event-free survival at 36 months was 84.5% in the pembrolizumab-chemotherapy group, compared with 76.8% in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% confidence interval, 0.48 to 0.82; P <0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.
At the first interim analysis, 64.8% achieved pathological complete response in the pembrolizumab group versus 51.2% in the placebo group. At the fourth interim analysis at 36 months, event-free survival was 76.8% in the placebo arm and 84.5% in the pembrolizumab arm. RCB-0 status was achieved by 63.4% and 56.2% of patients in the pembrolizumab and placebo arms, respectively.
Pembrolizumab did contribute immune-related adverse events, mostly grades 1-2, in about 17% of patients with thyroid function abnormalities most common with most occurring 20 weeks prior to surgical treatment.
Treatment with pembrolizumab added to chemotherapy, compared with chemotherapy alone, shifted residual cancer burden to lower categories across the entire spectrum of patients in the trial.
The hazard ratio for event-free survival with RCB-0, which Dr. Pusztai said is equivalent to a pathologic complete response (pCR), was 0.70 (0.38-1.31). For RCB-1 (minimal residual disease) it was 0.92 (0.39-2.20); for RCB-2 (moderate residual disease) it was 0.52 (0.32-0.82); and for RCB-3 (extensive residual disease) it was 1.24 (0.69-2.23).
“The most important finding is that patients in RCB-2, a group with a moderate amount of residual disease, experienced significant improvement with pembrolizumab. This clearly indicates not only that pembrolizumab leads to higher pCR rates but also that the pembrolizumCR/RCB-0 ... extends to patients who do not achieve pCR,” Dr. Pusztai said.
The benefit, he suggested, could be a result of the adjuvant pembrolizumab maintenance phase.
Patients in the RCB-3 category do poorly regardless of treatment (EFS of 34.6 % and 26.2% in the pembrolizumab and placebo arms, respectively).
“The RCB-3 population represents an unmet medical need, and they will need better drugs, and additional postoperative adjuvant therapy,” Dr. Pusztai said. The current standard of care is capecitabine for 6-8 cycles. Emerging new therapies, such as antibody drug conjugates, will be tested, he said.
In terms of limitations, adjuvant capecitabine was not allowed. “It remains uncertain how much better the RCB-2 and -3 patient outcomes would have been if capecitabine were administered,” he said.
The study was funded by Merck Sharp and Dohme, a subsidiary of Merck. Dr. Pusztai has received consulting fees and honoraria from Merck.
for improving survival in patients with early triple negative breast cancer (TNBC).
The findings were presented in Chicago June 4 and 5 at the annual meeting of the American Society of Clinical Oncology by study author Lajos Pusztai, MD, D.Phil, director of Breast Cancer Translational Research at Yale University, New Haven, Conn.
KEYNOTE-522 is the first prospective, randomized, placebo-controlled phase 3 trial of pembrolizumab for early-stage TNBC in the neoadjuvant and adjuvant setting.
The study included 1,174 patients (median age 49 years) with previously untreated stage II or III triple-negative breast cancer. Patients were randomly assigned to receive neoadjuvant therapy with four cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After surgery, patients received pembrolizumab or placebeo for 9 cycles or until recurrence or unacceptable toxicity. The primary end points were pathological complete response and event-free survival.
A total of 784 patients were treated with pembrolizumab and chemotherapy, and the second group of 390 patients received a placebo and chemotherapy. After surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo and chemotherapy for every 3 weeks for up to nine cycles.
The estimated event-free survival at 36 months was 84.5% in the pembrolizumab-chemotherapy group, compared with 76.8% in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% confidence interval, 0.48 to 0.82; P <0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.
At the first interim analysis, 64.8% achieved pathological complete response in the pembrolizumab group versus 51.2% in the placebo group. At the fourth interim analysis at 36 months, event-free survival was 76.8% in the placebo arm and 84.5% in the pembrolizumab arm. RCB-0 status was achieved by 63.4% and 56.2% of patients in the pembrolizumab and placebo arms, respectively.
Pembrolizumab did contribute immune-related adverse events, mostly grades 1-2, in about 17% of patients with thyroid function abnormalities most common with most occurring 20 weeks prior to surgical treatment.
Treatment with pembrolizumab added to chemotherapy, compared with chemotherapy alone, shifted residual cancer burden to lower categories across the entire spectrum of patients in the trial.
The hazard ratio for event-free survival with RCB-0, which Dr. Pusztai said is equivalent to a pathologic complete response (pCR), was 0.70 (0.38-1.31). For RCB-1 (minimal residual disease) it was 0.92 (0.39-2.20); for RCB-2 (moderate residual disease) it was 0.52 (0.32-0.82); and for RCB-3 (extensive residual disease) it was 1.24 (0.69-2.23).
“The most important finding is that patients in RCB-2, a group with a moderate amount of residual disease, experienced significant improvement with pembrolizumab. This clearly indicates not only that pembrolizumab leads to higher pCR rates but also that the pembrolizumCR/RCB-0 ... extends to patients who do not achieve pCR,” Dr. Pusztai said.
The benefit, he suggested, could be a result of the adjuvant pembrolizumab maintenance phase.
Patients in the RCB-3 category do poorly regardless of treatment (EFS of 34.6 % and 26.2% in the pembrolizumab and placebo arms, respectively).
“The RCB-3 population represents an unmet medical need, and they will need better drugs, and additional postoperative adjuvant therapy,” Dr. Pusztai said. The current standard of care is capecitabine for 6-8 cycles. Emerging new therapies, such as antibody drug conjugates, will be tested, he said.
In terms of limitations, adjuvant capecitabine was not allowed. “It remains uncertain how much better the RCB-2 and -3 patient outcomes would have been if capecitabine were administered,” he said.
The study was funded by Merck Sharp and Dohme, a subsidiary of Merck. Dr. Pusztai has received consulting fees and honoraria from Merck.
FROM ASCO 2022
‘Very impressive’ data promise new blood cancer option
“We have limited treatment options for triple-class exposed and refractory multiple myeloma patients, especially for use in the community,” coauthor Dr. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center, New York, said in an interview. “Teclistamab is a BCMA directed bispecific antibody that is showing high response rates at the recommended subcutaneous phase 2 doses (RP2D),” and has a strong safety profile, he explained.
Teclistamab tackles two targets – both CD3 on the surface of T cells and B-cell maturation antigen (BCMA) on the surface of myeloma cells – said Dr. Ajay K. Nooka of Emory University, Atlanta, in the meeting presentation. The study was published simultaneously in the New England Journal of Medicine.
After teclistamab showed promising efficacy and an acceptable level of side effects in phase 1, researchers enrolled 165 adults aged 33-84 years with relapsed or refractory multiple myeloma (MM). The patients had experienced at least three previous lines of therapy (LOT). All patients received a weekly subcutaneous injection of 1.5 mg/kg of body weight following step-up doses of 0.06 mg/kg and 0.3 mg/kg. The primary endpoint of the study was overall response.
The median age of the patients was 64 years; 58% were male, 81.2% were White. The median prior LOT was 5; all of the patients were triple-class exposed (100%); 70% were penta-drug exposed, 78% were triple-class refractory, and 30% penta-drug refractory.
The overall response rate (ORR) was 63% over a median follow-up period of approximately 14.1 months. In addition, 39.4% of patients had a complete response or better, and 26.7% had no minimal residual disease, for a negative minimal residual disease rate of 46.2% in patients with complete response. The median durations of response and progression-free survival were 18.4 months and 11.3 months, respectively.
“The ORR was consistent across clinically relevant subgroups, including high cytogenetic risk and penta-drug refractory subgroups,” Dr. Nooka said in his presentation.
The most common adverse event was cytokine release syndrome, which occurred in 72.1% of patients; however, only 0.6% of these events were grade 3, and none were grade 4. Other adverse events included neutropenia in 70.9% (64.2% of events were grade 3 or 4), anemia (52.1%, 37.0% of events were grade 3 or 4, respectively) and thrombocytopenia (40%, 21.2% of events were grade 3 or 4). Infections occurred in 76.4% of patients overall, 44.8% of which were grade 3 or 4, and neurotoxic events occurred in 24 patients (14.5%). The five cases of immune effector cell–associated neurotoxicity syndrome (CRS) were grade 1 or 2.
A total of 2 patients (1.2%) discontinued the study because of adverse events, but no discontinuations or dose reductions occurred as a result of neurotoxic events.
A total of 5 deaths attributed to teclistamab occurred during the study: 2 caused by COVID-19, 1 pneumonia, 1 hepatic failure, and 1 progressive multifocal leukoencephalopathy (PML).
The responses were durable and persisted over time, said Dr. Nooka. At the point of data cutoff, 64.4% of patients who responded maintained that response.
Overall, the data support teclistamab as “a promising new, off-the-shelf, T-cell redirecting therapy targeting BCMA for patients with relapsed or refractory MM,” with phase 3 studies ongoing and early access programs in progress, Dr. Nooka concluded.
“The ORR and durability of response seen with teclistamab is very impressive when one sees the data for other single agents approved for relapsed/refractory MM in the past,” Dr. Usmani said in an interview. “I hope the current data will help get a regulatory approval for the triple class exposed MM population.”
However, potential barriers to widespread use of teclistamab in practice include logistics and a learning curve for practicing hematologists/oncologists, Dr. Usmani noted. “While the CRS appears to be grade 1 or 2 and very manageable, the logistics of giving bispecific antibodies in the community setting and managing CRS during the first cycle of therapy in the community will need to be worked out, and partnership with academic centers that have experience in managing these patients will be needed, he added.
As for additional research, “teclistamab is being combined with other MM therapies and being explored in earlier lines of treatment,” Dr. Usmani said.
Be ready to manage infections
Despite promising early findings, the use of teclistamab and other BCMA-targeting biospecific therapies is “not a free lunch” for refractory and relapsed MM patients, said discussant Dr. Madhav V. Dhodapkar of Emory University, Atlanta, during the discussion period after the ASCO presentation.
Although the risk of CRS and ICANS appears low, “infections are emerging as a major adverse event” that need to be recognized and managed, he said.
A distinct pattern of infections may be emerging, based on data from the current study and other studies of similar therapies, with infections such as Pneumocystis jirovecii (PJP) and cytomegalovirus (CMV) reactivation, Dr. Dhodapkar added.
He noted other considerations for studies of teclistamab and similar therapies, including the need to address both host-related and tumor-related factors, as well as seasonal and opportunistic threats such as COVID-19.
Future research questions include whether there is a role for pathogen-specific surveillance to help mitigate infection risk, including COVID-19 risk management strategies, he emphasized.
The study was funded by Janssen Research and Development.
Dr. Usmani disclosed relationships as a consultant or advisor, speakers’ bureau member, and/or recipient of research funding from serving as a consultant or advisor for Abbvie, Amgen, Bristol-Myers Squibb/Celgene, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen Oncology, Karyopharm Therapeutics, Merck, Oncopeptides, Seattle Genetics, Skyline Diagnostics, and Takeda. Lead author of the New England Journal paper Dr. Philippe Moreau disclosed relationships with companies including Abbvie, Amgen, Celgene, GlaxoSmithKline, Janssen-Cilag, Oncopeptides, and Sanofi. ASCO presenting author Dr. Nooka disclosed relationships with companies including Adaptive Biotechnologies, Amgen, BeyondSpring Pharmaceuticals, Bristol-Myers Squibb/Celgene, Genzyme, GlaxoSmithKline, Janssen Oncology, Karyopharm Therapeutics, Oncopeptides, Secura Bio, Arch Oncology, and Takeda.
“We have limited treatment options for triple-class exposed and refractory multiple myeloma patients, especially for use in the community,” coauthor Dr. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center, New York, said in an interview. “Teclistamab is a BCMA directed bispecific antibody that is showing high response rates at the recommended subcutaneous phase 2 doses (RP2D),” and has a strong safety profile, he explained.
Teclistamab tackles two targets – both CD3 on the surface of T cells and B-cell maturation antigen (BCMA) on the surface of myeloma cells – said Dr. Ajay K. Nooka of Emory University, Atlanta, in the meeting presentation. The study was published simultaneously in the New England Journal of Medicine.
After teclistamab showed promising efficacy and an acceptable level of side effects in phase 1, researchers enrolled 165 adults aged 33-84 years with relapsed or refractory multiple myeloma (MM). The patients had experienced at least three previous lines of therapy (LOT). All patients received a weekly subcutaneous injection of 1.5 mg/kg of body weight following step-up doses of 0.06 mg/kg and 0.3 mg/kg. The primary endpoint of the study was overall response.
The median age of the patients was 64 years; 58% were male, 81.2% were White. The median prior LOT was 5; all of the patients were triple-class exposed (100%); 70% were penta-drug exposed, 78% were triple-class refractory, and 30% penta-drug refractory.
The overall response rate (ORR) was 63% over a median follow-up period of approximately 14.1 months. In addition, 39.4% of patients had a complete response or better, and 26.7% had no minimal residual disease, for a negative minimal residual disease rate of 46.2% in patients with complete response. The median durations of response and progression-free survival were 18.4 months and 11.3 months, respectively.
“The ORR was consistent across clinically relevant subgroups, including high cytogenetic risk and penta-drug refractory subgroups,” Dr. Nooka said in his presentation.
The most common adverse event was cytokine release syndrome, which occurred in 72.1% of patients; however, only 0.6% of these events were grade 3, and none were grade 4. Other adverse events included neutropenia in 70.9% (64.2% of events were grade 3 or 4), anemia (52.1%, 37.0% of events were grade 3 or 4, respectively) and thrombocytopenia (40%, 21.2% of events were grade 3 or 4). Infections occurred in 76.4% of patients overall, 44.8% of which were grade 3 or 4, and neurotoxic events occurred in 24 patients (14.5%). The five cases of immune effector cell–associated neurotoxicity syndrome (CRS) were grade 1 or 2.
A total of 2 patients (1.2%) discontinued the study because of adverse events, but no discontinuations or dose reductions occurred as a result of neurotoxic events.
A total of 5 deaths attributed to teclistamab occurred during the study: 2 caused by COVID-19, 1 pneumonia, 1 hepatic failure, and 1 progressive multifocal leukoencephalopathy (PML).
The responses were durable and persisted over time, said Dr. Nooka. At the point of data cutoff, 64.4% of patients who responded maintained that response.
Overall, the data support teclistamab as “a promising new, off-the-shelf, T-cell redirecting therapy targeting BCMA for patients with relapsed or refractory MM,” with phase 3 studies ongoing and early access programs in progress, Dr. Nooka concluded.
“The ORR and durability of response seen with teclistamab is very impressive when one sees the data for other single agents approved for relapsed/refractory MM in the past,” Dr. Usmani said in an interview. “I hope the current data will help get a regulatory approval for the triple class exposed MM population.”
However, potential barriers to widespread use of teclistamab in practice include logistics and a learning curve for practicing hematologists/oncologists, Dr. Usmani noted. “While the CRS appears to be grade 1 or 2 and very manageable, the logistics of giving bispecific antibodies in the community setting and managing CRS during the first cycle of therapy in the community will need to be worked out, and partnership with academic centers that have experience in managing these patients will be needed, he added.
As for additional research, “teclistamab is being combined with other MM therapies and being explored in earlier lines of treatment,” Dr. Usmani said.
Be ready to manage infections
Despite promising early findings, the use of teclistamab and other BCMA-targeting biospecific therapies is “not a free lunch” for refractory and relapsed MM patients, said discussant Dr. Madhav V. Dhodapkar of Emory University, Atlanta, during the discussion period after the ASCO presentation.
Although the risk of CRS and ICANS appears low, “infections are emerging as a major adverse event” that need to be recognized and managed, he said.
A distinct pattern of infections may be emerging, based on data from the current study and other studies of similar therapies, with infections such as Pneumocystis jirovecii (PJP) and cytomegalovirus (CMV) reactivation, Dr. Dhodapkar added.
He noted other considerations for studies of teclistamab and similar therapies, including the need to address both host-related and tumor-related factors, as well as seasonal and opportunistic threats such as COVID-19.
Future research questions include whether there is a role for pathogen-specific surveillance to help mitigate infection risk, including COVID-19 risk management strategies, he emphasized.
The study was funded by Janssen Research and Development.
Dr. Usmani disclosed relationships as a consultant or advisor, speakers’ bureau member, and/or recipient of research funding from serving as a consultant or advisor for Abbvie, Amgen, Bristol-Myers Squibb/Celgene, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen Oncology, Karyopharm Therapeutics, Merck, Oncopeptides, Seattle Genetics, Skyline Diagnostics, and Takeda. Lead author of the New England Journal paper Dr. Philippe Moreau disclosed relationships with companies including Abbvie, Amgen, Celgene, GlaxoSmithKline, Janssen-Cilag, Oncopeptides, and Sanofi. ASCO presenting author Dr. Nooka disclosed relationships with companies including Adaptive Biotechnologies, Amgen, BeyondSpring Pharmaceuticals, Bristol-Myers Squibb/Celgene, Genzyme, GlaxoSmithKline, Janssen Oncology, Karyopharm Therapeutics, Oncopeptides, Secura Bio, Arch Oncology, and Takeda.
“We have limited treatment options for triple-class exposed and refractory multiple myeloma patients, especially for use in the community,” coauthor Dr. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center, New York, said in an interview. “Teclistamab is a BCMA directed bispecific antibody that is showing high response rates at the recommended subcutaneous phase 2 doses (RP2D),” and has a strong safety profile, he explained.
Teclistamab tackles two targets – both CD3 on the surface of T cells and B-cell maturation antigen (BCMA) on the surface of myeloma cells – said Dr. Ajay K. Nooka of Emory University, Atlanta, in the meeting presentation. The study was published simultaneously in the New England Journal of Medicine.
After teclistamab showed promising efficacy and an acceptable level of side effects in phase 1, researchers enrolled 165 adults aged 33-84 years with relapsed or refractory multiple myeloma (MM). The patients had experienced at least three previous lines of therapy (LOT). All patients received a weekly subcutaneous injection of 1.5 mg/kg of body weight following step-up doses of 0.06 mg/kg and 0.3 mg/kg. The primary endpoint of the study was overall response.
The median age of the patients was 64 years; 58% were male, 81.2% were White. The median prior LOT was 5; all of the patients were triple-class exposed (100%); 70% were penta-drug exposed, 78% were triple-class refractory, and 30% penta-drug refractory.
The overall response rate (ORR) was 63% over a median follow-up period of approximately 14.1 months. In addition, 39.4% of patients had a complete response or better, and 26.7% had no minimal residual disease, for a negative minimal residual disease rate of 46.2% in patients with complete response. The median durations of response and progression-free survival were 18.4 months and 11.3 months, respectively.
“The ORR was consistent across clinically relevant subgroups, including high cytogenetic risk and penta-drug refractory subgroups,” Dr. Nooka said in his presentation.
The most common adverse event was cytokine release syndrome, which occurred in 72.1% of patients; however, only 0.6% of these events were grade 3, and none were grade 4. Other adverse events included neutropenia in 70.9% (64.2% of events were grade 3 or 4), anemia (52.1%, 37.0% of events were grade 3 or 4, respectively) and thrombocytopenia (40%, 21.2% of events were grade 3 or 4). Infections occurred in 76.4% of patients overall, 44.8% of which were grade 3 or 4, and neurotoxic events occurred in 24 patients (14.5%). The five cases of immune effector cell–associated neurotoxicity syndrome (CRS) were grade 1 or 2.
A total of 2 patients (1.2%) discontinued the study because of adverse events, but no discontinuations or dose reductions occurred as a result of neurotoxic events.
A total of 5 deaths attributed to teclistamab occurred during the study: 2 caused by COVID-19, 1 pneumonia, 1 hepatic failure, and 1 progressive multifocal leukoencephalopathy (PML).
The responses were durable and persisted over time, said Dr. Nooka. At the point of data cutoff, 64.4% of patients who responded maintained that response.
Overall, the data support teclistamab as “a promising new, off-the-shelf, T-cell redirecting therapy targeting BCMA for patients with relapsed or refractory MM,” with phase 3 studies ongoing and early access programs in progress, Dr. Nooka concluded.
“The ORR and durability of response seen with teclistamab is very impressive when one sees the data for other single agents approved for relapsed/refractory MM in the past,” Dr. Usmani said in an interview. “I hope the current data will help get a regulatory approval for the triple class exposed MM population.”
However, potential barriers to widespread use of teclistamab in practice include logistics and a learning curve for practicing hematologists/oncologists, Dr. Usmani noted. “While the CRS appears to be grade 1 or 2 and very manageable, the logistics of giving bispecific antibodies in the community setting and managing CRS during the first cycle of therapy in the community will need to be worked out, and partnership with academic centers that have experience in managing these patients will be needed, he added.
As for additional research, “teclistamab is being combined with other MM therapies and being explored in earlier lines of treatment,” Dr. Usmani said.
Be ready to manage infections
Despite promising early findings, the use of teclistamab and other BCMA-targeting biospecific therapies is “not a free lunch” for refractory and relapsed MM patients, said discussant Dr. Madhav V. Dhodapkar of Emory University, Atlanta, during the discussion period after the ASCO presentation.
Although the risk of CRS and ICANS appears low, “infections are emerging as a major adverse event” that need to be recognized and managed, he said.
A distinct pattern of infections may be emerging, based on data from the current study and other studies of similar therapies, with infections such as Pneumocystis jirovecii (PJP) and cytomegalovirus (CMV) reactivation, Dr. Dhodapkar added.
He noted other considerations for studies of teclistamab and similar therapies, including the need to address both host-related and tumor-related factors, as well as seasonal and opportunistic threats such as COVID-19.
Future research questions include whether there is a role for pathogen-specific surveillance to help mitigate infection risk, including COVID-19 risk management strategies, he emphasized.
The study was funded by Janssen Research and Development.
Dr. Usmani disclosed relationships as a consultant or advisor, speakers’ bureau member, and/or recipient of research funding from serving as a consultant or advisor for Abbvie, Amgen, Bristol-Myers Squibb/Celgene, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen Oncology, Karyopharm Therapeutics, Merck, Oncopeptides, Seattle Genetics, Skyline Diagnostics, and Takeda. Lead author of the New England Journal paper Dr. Philippe Moreau disclosed relationships with companies including Abbvie, Amgen, Celgene, GlaxoSmithKline, Janssen-Cilag, Oncopeptides, and Sanofi. ASCO presenting author Dr. Nooka disclosed relationships with companies including Adaptive Biotechnologies, Amgen, BeyondSpring Pharmaceuticals, Bristol-Myers Squibb/Celgene, Genzyme, GlaxoSmithKline, Janssen Oncology, Karyopharm Therapeutics, Oncopeptides, Secura Bio, Arch Oncology, and Takeda.
FROM ASCO 2022
New treatment outperforms chemo in HER2-low breast cancer
CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan.
“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.
“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.
The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.
However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.
Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.
The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).
Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.
Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.
The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.
CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan.
“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.
“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.
The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.
However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.
Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.
The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).
Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.
Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.
The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.
CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan.
“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.
“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.
The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.
However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.
Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.
The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).
Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.
Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.
The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.
AT ASCO 2022
New treatment meets unmet need in breast cancer
CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.
The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.
The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.
“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.
The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.
Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.
The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.
“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.
Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.
The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).
Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).
Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.
CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.
The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.
The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.
“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.
The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.
Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.
The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.
“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.
Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.
The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).
Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).
Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.
CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.
The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.
The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.
“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.
The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.
Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.
The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.
“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.
Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.
The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).
Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).
Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.
AT ASCO 2022
ctDNA spots breast cancer recurrence
CHICAGO -- Circulating tumor DNA successfully identified minimal residual disease in patients with hormone receptor-positive (HR+) breast cancer who are at high risk for recurrence – generally years before metastases occurs. The findings come from the CHiRP study, which included patients who were at least 5 years post diagnosis.
The researchers and other groups previously showed that minimal residual disease (MRD) status is associated with distant-recurrence free survival, “yet little is known about ctDNA in the late adjuvant setting in hormone receptor-positive breast cancer,” said Marla Lipsyc-Sharf, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston. Dr. Lipsyc-Sharf presented her findings June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology.
The study was simultaneously published online in the Journal of Clinical Oncology.
Plasma samples were collected at follow-up visits every 6-12 months, and a personalized version of the RaDaR assay was used to detect ctDNA associated with MRD. Although the technology is currently only useful for research, the team hopes it can soon provide clinical guidance. “The CHiRP study is an important first step toward an understanding of the baseline prevalence and role of ctDNA in this setting. Multiple prospective clinical trials are underway or beginning to establish the clinical utility of ctDNA assays in this setting and understand whether intervention after MRD detection improves patient outcomes, such as survival or quality of life,” she said.
Ben Ho Park, MD, PhD, an oncologist with Vanderbilt University Medical Center, Nashville, Tenn., described the findings as encouraging.
“I think most of us saw this very striking data that you could actually predict who’s going to recur and that all patients who did recur were ctDNA positive. The numbers are really, indeed very encouraging that we can develop assays now that detect minimal residual disease with serum monitoring. It really opens up the floodgates for designing studies [to determine] who to treat with additional adjuvant therapies while they’re still in the adjuvant phase of breast cancer therapy,” Dr. Park said during a discussion that followed the presentation.
The study included 83 patients with high-risk HR+ breast cancer and no evidence of recurrence within 5 years of diagnosis. High risk was defined as T3/T4 and/or N2/N3 disease; T1/N1 disease with 3 or more lymph nodes involved; or T2N1 disease with Ki67 ≥ 20%, grade 3, or oncotype DX score ≥ 26.
For each patient, clinicians designed a tumor-informed liquid biopsy assay to detect plasma ctDNA. A total of 68.7% of participants had stage 3 disease. A total of 90.4% received curative-intent chemotherapy, and all received endocrine therapy. A total of 47% remained on endocrine therapy at their last follow-up.
A total of 93.2% of patients who completed adjuvant endocrine therapy had at least 5 years of treatment. A median of 8.4 years elapsed between diagnosis and first ctDNA sample, and the median follow-up was 10.4 years from diagnosis and 1.8 years from the first sample.
A total of 5% of patients had MRD when they entered the study, and 10% were found to have MRD at any time. Of 6 patients (7.2%) who experienced a metastatic recurrence, all were MRD+, and ctDNA evidence appeared as soon as 37.6 months before diagnosis (median 12.4 months). Of eight patients who were MRD+ at some point, two of them had not had a recurrence at the latest follow-up, and one patient had no follow-up at all, and the other had a follow-up 15.4 months after ctDNA detection.
Limitations of the study included a limited follow-up period and low rate of recurrence, as well as infrequent plasma sampling.
Dr. Lipsyc-Sharf has no relevant financial disclosures. Dr. Park has financial relationships and/or has received funding from Celcuity, Loxo, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, Abbvie, GE Healthcare, Lilly, Pfizer, Horizon Discovery, and Tempus.
CHICAGO -- Circulating tumor DNA successfully identified minimal residual disease in patients with hormone receptor-positive (HR+) breast cancer who are at high risk for recurrence – generally years before metastases occurs. The findings come from the CHiRP study, which included patients who were at least 5 years post diagnosis.
The researchers and other groups previously showed that minimal residual disease (MRD) status is associated with distant-recurrence free survival, “yet little is known about ctDNA in the late adjuvant setting in hormone receptor-positive breast cancer,” said Marla Lipsyc-Sharf, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston. Dr. Lipsyc-Sharf presented her findings June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology.
The study was simultaneously published online in the Journal of Clinical Oncology.
Plasma samples were collected at follow-up visits every 6-12 months, and a personalized version of the RaDaR assay was used to detect ctDNA associated with MRD. Although the technology is currently only useful for research, the team hopes it can soon provide clinical guidance. “The CHiRP study is an important first step toward an understanding of the baseline prevalence and role of ctDNA in this setting. Multiple prospective clinical trials are underway or beginning to establish the clinical utility of ctDNA assays in this setting and understand whether intervention after MRD detection improves patient outcomes, such as survival or quality of life,” she said.
Ben Ho Park, MD, PhD, an oncologist with Vanderbilt University Medical Center, Nashville, Tenn., described the findings as encouraging.
“I think most of us saw this very striking data that you could actually predict who’s going to recur and that all patients who did recur were ctDNA positive. The numbers are really, indeed very encouraging that we can develop assays now that detect minimal residual disease with serum monitoring. It really opens up the floodgates for designing studies [to determine] who to treat with additional adjuvant therapies while they’re still in the adjuvant phase of breast cancer therapy,” Dr. Park said during a discussion that followed the presentation.
The study included 83 patients with high-risk HR+ breast cancer and no evidence of recurrence within 5 years of diagnosis. High risk was defined as T3/T4 and/or N2/N3 disease; T1/N1 disease with 3 or more lymph nodes involved; or T2N1 disease with Ki67 ≥ 20%, grade 3, or oncotype DX score ≥ 26.
For each patient, clinicians designed a tumor-informed liquid biopsy assay to detect plasma ctDNA. A total of 68.7% of participants had stage 3 disease. A total of 90.4% received curative-intent chemotherapy, and all received endocrine therapy. A total of 47% remained on endocrine therapy at their last follow-up.
A total of 93.2% of patients who completed adjuvant endocrine therapy had at least 5 years of treatment. A median of 8.4 years elapsed between diagnosis and first ctDNA sample, and the median follow-up was 10.4 years from diagnosis and 1.8 years from the first sample.
A total of 5% of patients had MRD when they entered the study, and 10% were found to have MRD at any time. Of 6 patients (7.2%) who experienced a metastatic recurrence, all were MRD+, and ctDNA evidence appeared as soon as 37.6 months before diagnosis (median 12.4 months). Of eight patients who were MRD+ at some point, two of them had not had a recurrence at the latest follow-up, and one patient had no follow-up at all, and the other had a follow-up 15.4 months after ctDNA detection.
Limitations of the study included a limited follow-up period and low rate of recurrence, as well as infrequent plasma sampling.
Dr. Lipsyc-Sharf has no relevant financial disclosures. Dr. Park has financial relationships and/or has received funding from Celcuity, Loxo, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, Abbvie, GE Healthcare, Lilly, Pfizer, Horizon Discovery, and Tempus.
CHICAGO -- Circulating tumor DNA successfully identified minimal residual disease in patients with hormone receptor-positive (HR+) breast cancer who are at high risk for recurrence – generally years before metastases occurs. The findings come from the CHiRP study, which included patients who were at least 5 years post diagnosis.
The researchers and other groups previously showed that minimal residual disease (MRD) status is associated with distant-recurrence free survival, “yet little is known about ctDNA in the late adjuvant setting in hormone receptor-positive breast cancer,” said Marla Lipsyc-Sharf, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston. Dr. Lipsyc-Sharf presented her findings June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology.
The study was simultaneously published online in the Journal of Clinical Oncology.
Plasma samples were collected at follow-up visits every 6-12 months, and a personalized version of the RaDaR assay was used to detect ctDNA associated with MRD. Although the technology is currently only useful for research, the team hopes it can soon provide clinical guidance. “The CHiRP study is an important first step toward an understanding of the baseline prevalence and role of ctDNA in this setting. Multiple prospective clinical trials are underway or beginning to establish the clinical utility of ctDNA assays in this setting and understand whether intervention after MRD detection improves patient outcomes, such as survival or quality of life,” she said.
Ben Ho Park, MD, PhD, an oncologist with Vanderbilt University Medical Center, Nashville, Tenn., described the findings as encouraging.
“I think most of us saw this very striking data that you could actually predict who’s going to recur and that all patients who did recur were ctDNA positive. The numbers are really, indeed very encouraging that we can develop assays now that detect minimal residual disease with serum monitoring. It really opens up the floodgates for designing studies [to determine] who to treat with additional adjuvant therapies while they’re still in the adjuvant phase of breast cancer therapy,” Dr. Park said during a discussion that followed the presentation.
The study included 83 patients with high-risk HR+ breast cancer and no evidence of recurrence within 5 years of diagnosis. High risk was defined as T3/T4 and/or N2/N3 disease; T1/N1 disease with 3 or more lymph nodes involved; or T2N1 disease with Ki67 ≥ 20%, grade 3, or oncotype DX score ≥ 26.
For each patient, clinicians designed a tumor-informed liquid biopsy assay to detect plasma ctDNA. A total of 68.7% of participants had stage 3 disease. A total of 90.4% received curative-intent chemotherapy, and all received endocrine therapy. A total of 47% remained on endocrine therapy at their last follow-up.
A total of 93.2% of patients who completed adjuvant endocrine therapy had at least 5 years of treatment. A median of 8.4 years elapsed between diagnosis and first ctDNA sample, and the median follow-up was 10.4 years from diagnosis and 1.8 years from the first sample.
A total of 5% of patients had MRD when they entered the study, and 10% were found to have MRD at any time. Of 6 patients (7.2%) who experienced a metastatic recurrence, all were MRD+, and ctDNA evidence appeared as soon as 37.6 months before diagnosis (median 12.4 months). Of eight patients who were MRD+ at some point, two of them had not had a recurrence at the latest follow-up, and one patient had no follow-up at all, and the other had a follow-up 15.4 months after ctDNA detection.
Limitations of the study included a limited follow-up period and low rate of recurrence, as well as infrequent plasma sampling.
Dr. Lipsyc-Sharf has no relevant financial disclosures. Dr. Park has financial relationships and/or has received funding from Celcuity, Loxo, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, Abbvie, GE Healthcare, Lilly, Pfizer, Horizon Discovery, and Tempus.
AT ASCO 2022
Improved survival in subset of advanced pancreatic cancer
, offering hope of a clinical advance in a cancer that remains very difficult to treat.
The drug is nimotuzumab, developed as a joint Chinese-Cuban venture, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), inhibiting tumor cells that overexpress EGFR.
When nimotuzumab was added to gemcitabine, it significantly improved overall survival, compared with gemcitabine alone, in a trial conducted in China in 92 patients with advanced pancreatic cancer who had KRAS wild-type tumors.
One-year survival rates were 43.6% with nimotuzumab versus 26.8% with placebo, while 3-year survival rates were 13.9% versus 2.7%.
The results were presented at the annual meeting of the American Society of Clinical Oncology and highlighted at a press briefing.
“We believe our NOTABLE trial will be a breakthrough in the field of pancreatic cancer,” co-lead author Shukui Qin, MD, department of medical oncology, Cancer Center, Jinling Hospital, Nanjing, China, commented in an ASCO press release.
“The outcomes in this trial may bring new hope to patients with KRAS wild-type pancreatic cancer,” he added.
“To see any survival benefit in a trial for metastatic pancreatic cancer is of interest,” commented Cathy Eng, MD, an ASCO expert in gastrointestinal cancers.
However, she pointed out that the subgroup of patients who may benefit is small – KRAS wild-type tumors are found in fewer than 10% of patients with pancreatic cancer.
“Additional studies in comparison with the combination of gemcitabine/nab-paclitaxel would be of interest,” Dr. Eng added, to validate “any potential advances to make a true difference in the lives of all patients with pancreatic cancer.”
Already marketed in China
Nimotuzumab is already marketed in China: It was approved in 2008 by the Chinese National Medical Products Administration for the treatment of nasopharyngeal carcinoma and is currently being investigated in head and neck, cervical, esophageal, and other cancers.
Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, commented in an interview that it will be “interesting to see the U.S. Food and Drug Administration’s response to the current data.”
She explained that the FDA has recently rejected drugs developed and tested in China, mostly notably sintilimab in non–small cell lung cancer, because the clinical data submitted were from China and not “reflective of the U.S. cancer population” and also because in this case there were already a number of other similar drugs available in this therapeutic area.
However, pancreatic cancer represents an unmet clinical need, which is a different situation, and there may be some consideration for an accelerated approval while awaiting a U.S. clinical trial, she speculated.
This trial showed an interesting proof of principle, she added – it showed that an EGRF inhibitor was active in KRAS wild-type advanced pancreatic cancer. This opens the door for exploration with other drugs that also act as EGFR blockers, as well as drugs with other actions such as BRAF antagonists, MAP kinase inhibitors, and/or immunotherapy.
Study details
The phase 3 NOTABLE trial involved 92 Chinese patients with locally advanced or metastatic KRAS wild-type pancreatic cancer randomized to nimotuzumab weekly or placebo plus gemcitabine until progression or unacceptable toxicity.
Median overall survival was significantly longer with nimotuzumab, at 10.9 versus 8.5 months with placebo, at a hazard ratio of 0.50.
The results showed that median progression-free survival (PFS) was also significantly longer among patients given nimotuzumab, at 4.2 versus 3.6 months in the placebo group, or a hazard ratio of 0.56.
Patients were then stratified based on whether they needed surgery to remove bile duct obstructions prior to chemotherapy, as those not requiring surgery tend to have better liver function and so may better tolerate chemotherapy.
The overall survival benefit with nimotuzumab was greater among patients with no surgical history, at 15.8 versus 6.0 months with placebo, at a hazard ratio of 0.40, compared with 11.9 versus 8.5 months among those with biliary obstruction, at a hazard ratio of 0.54.
Patients who did not receive treatment for biliary obstruction had a significantly longer PFS than those who underwent surgery, at 5.5 versus 3.4 months (P = .008).
The researchers report that the incidence of adverse events in the nimotuzumab group was similar to that among patients given placebo.
The most common grade 3 treatment-related adverse events with the combination therapy were neutropenia, in 11.1% of patients, leukopenia (8.9%), and thrombocytopenia (6.7%). There were no grade 4 adverse events.
The study was sponsored by Biotech Pharmaceutical. Dr. Qin has disclosed no relevant financial relationships. Dr. Eng has disclosed relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer. Dr. Gralow has disclosed relationships with Genentech, AstraZeneca, Hexal, Puma Biotechnology, Roche, Novartis, Seagen, and Genomic Health.
A version of this article first appeared on Medscape.com.
, offering hope of a clinical advance in a cancer that remains very difficult to treat.
The drug is nimotuzumab, developed as a joint Chinese-Cuban venture, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), inhibiting tumor cells that overexpress EGFR.
When nimotuzumab was added to gemcitabine, it significantly improved overall survival, compared with gemcitabine alone, in a trial conducted in China in 92 patients with advanced pancreatic cancer who had KRAS wild-type tumors.
One-year survival rates were 43.6% with nimotuzumab versus 26.8% with placebo, while 3-year survival rates were 13.9% versus 2.7%.
The results were presented at the annual meeting of the American Society of Clinical Oncology and highlighted at a press briefing.
“We believe our NOTABLE trial will be a breakthrough in the field of pancreatic cancer,” co-lead author Shukui Qin, MD, department of medical oncology, Cancer Center, Jinling Hospital, Nanjing, China, commented in an ASCO press release.
“The outcomes in this trial may bring new hope to patients with KRAS wild-type pancreatic cancer,” he added.
“To see any survival benefit in a trial for metastatic pancreatic cancer is of interest,” commented Cathy Eng, MD, an ASCO expert in gastrointestinal cancers.
However, she pointed out that the subgroup of patients who may benefit is small – KRAS wild-type tumors are found in fewer than 10% of patients with pancreatic cancer.
“Additional studies in comparison with the combination of gemcitabine/nab-paclitaxel would be of interest,” Dr. Eng added, to validate “any potential advances to make a true difference in the lives of all patients with pancreatic cancer.”
Already marketed in China
Nimotuzumab is already marketed in China: It was approved in 2008 by the Chinese National Medical Products Administration for the treatment of nasopharyngeal carcinoma and is currently being investigated in head and neck, cervical, esophageal, and other cancers.
Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, commented in an interview that it will be “interesting to see the U.S. Food and Drug Administration’s response to the current data.”
She explained that the FDA has recently rejected drugs developed and tested in China, mostly notably sintilimab in non–small cell lung cancer, because the clinical data submitted were from China and not “reflective of the U.S. cancer population” and also because in this case there were already a number of other similar drugs available in this therapeutic area.
However, pancreatic cancer represents an unmet clinical need, which is a different situation, and there may be some consideration for an accelerated approval while awaiting a U.S. clinical trial, she speculated.
This trial showed an interesting proof of principle, she added – it showed that an EGRF inhibitor was active in KRAS wild-type advanced pancreatic cancer. This opens the door for exploration with other drugs that also act as EGFR blockers, as well as drugs with other actions such as BRAF antagonists, MAP kinase inhibitors, and/or immunotherapy.
Study details
The phase 3 NOTABLE trial involved 92 Chinese patients with locally advanced or metastatic KRAS wild-type pancreatic cancer randomized to nimotuzumab weekly or placebo plus gemcitabine until progression or unacceptable toxicity.
Median overall survival was significantly longer with nimotuzumab, at 10.9 versus 8.5 months with placebo, at a hazard ratio of 0.50.
The results showed that median progression-free survival (PFS) was also significantly longer among patients given nimotuzumab, at 4.2 versus 3.6 months in the placebo group, or a hazard ratio of 0.56.
Patients were then stratified based on whether they needed surgery to remove bile duct obstructions prior to chemotherapy, as those not requiring surgery tend to have better liver function and so may better tolerate chemotherapy.
The overall survival benefit with nimotuzumab was greater among patients with no surgical history, at 15.8 versus 6.0 months with placebo, at a hazard ratio of 0.40, compared with 11.9 versus 8.5 months among those with biliary obstruction, at a hazard ratio of 0.54.
Patients who did not receive treatment for biliary obstruction had a significantly longer PFS than those who underwent surgery, at 5.5 versus 3.4 months (P = .008).
The researchers report that the incidence of adverse events in the nimotuzumab group was similar to that among patients given placebo.
The most common grade 3 treatment-related adverse events with the combination therapy were neutropenia, in 11.1% of patients, leukopenia (8.9%), and thrombocytopenia (6.7%). There were no grade 4 adverse events.
The study was sponsored by Biotech Pharmaceutical. Dr. Qin has disclosed no relevant financial relationships. Dr. Eng has disclosed relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer. Dr. Gralow has disclosed relationships with Genentech, AstraZeneca, Hexal, Puma Biotechnology, Roche, Novartis, Seagen, and Genomic Health.
A version of this article first appeared on Medscape.com.
, offering hope of a clinical advance in a cancer that remains very difficult to treat.
The drug is nimotuzumab, developed as a joint Chinese-Cuban venture, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), inhibiting tumor cells that overexpress EGFR.
When nimotuzumab was added to gemcitabine, it significantly improved overall survival, compared with gemcitabine alone, in a trial conducted in China in 92 patients with advanced pancreatic cancer who had KRAS wild-type tumors.
One-year survival rates were 43.6% with nimotuzumab versus 26.8% with placebo, while 3-year survival rates were 13.9% versus 2.7%.
The results were presented at the annual meeting of the American Society of Clinical Oncology and highlighted at a press briefing.
“We believe our NOTABLE trial will be a breakthrough in the field of pancreatic cancer,” co-lead author Shukui Qin, MD, department of medical oncology, Cancer Center, Jinling Hospital, Nanjing, China, commented in an ASCO press release.
“The outcomes in this trial may bring new hope to patients with KRAS wild-type pancreatic cancer,” he added.
“To see any survival benefit in a trial for metastatic pancreatic cancer is of interest,” commented Cathy Eng, MD, an ASCO expert in gastrointestinal cancers.
However, she pointed out that the subgroup of patients who may benefit is small – KRAS wild-type tumors are found in fewer than 10% of patients with pancreatic cancer.
“Additional studies in comparison with the combination of gemcitabine/nab-paclitaxel would be of interest,” Dr. Eng added, to validate “any potential advances to make a true difference in the lives of all patients with pancreatic cancer.”
Already marketed in China
Nimotuzumab is already marketed in China: It was approved in 2008 by the Chinese National Medical Products Administration for the treatment of nasopharyngeal carcinoma and is currently being investigated in head and neck, cervical, esophageal, and other cancers.
Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, commented in an interview that it will be “interesting to see the U.S. Food and Drug Administration’s response to the current data.”
She explained that the FDA has recently rejected drugs developed and tested in China, mostly notably sintilimab in non–small cell lung cancer, because the clinical data submitted were from China and not “reflective of the U.S. cancer population” and also because in this case there were already a number of other similar drugs available in this therapeutic area.
However, pancreatic cancer represents an unmet clinical need, which is a different situation, and there may be some consideration for an accelerated approval while awaiting a U.S. clinical trial, she speculated.
This trial showed an interesting proof of principle, she added – it showed that an EGRF inhibitor was active in KRAS wild-type advanced pancreatic cancer. This opens the door for exploration with other drugs that also act as EGFR blockers, as well as drugs with other actions such as BRAF antagonists, MAP kinase inhibitors, and/or immunotherapy.
Study details
The phase 3 NOTABLE trial involved 92 Chinese patients with locally advanced or metastatic KRAS wild-type pancreatic cancer randomized to nimotuzumab weekly or placebo plus gemcitabine until progression or unacceptable toxicity.
Median overall survival was significantly longer with nimotuzumab, at 10.9 versus 8.5 months with placebo, at a hazard ratio of 0.50.
The results showed that median progression-free survival (PFS) was also significantly longer among patients given nimotuzumab, at 4.2 versus 3.6 months in the placebo group, or a hazard ratio of 0.56.
Patients were then stratified based on whether they needed surgery to remove bile duct obstructions prior to chemotherapy, as those not requiring surgery tend to have better liver function and so may better tolerate chemotherapy.
The overall survival benefit with nimotuzumab was greater among patients with no surgical history, at 15.8 versus 6.0 months with placebo, at a hazard ratio of 0.40, compared with 11.9 versus 8.5 months among those with biliary obstruction, at a hazard ratio of 0.54.
Patients who did not receive treatment for biliary obstruction had a significantly longer PFS than those who underwent surgery, at 5.5 versus 3.4 months (P = .008).
The researchers report that the incidence of adverse events in the nimotuzumab group was similar to that among patients given placebo.
The most common grade 3 treatment-related adverse events with the combination therapy were neutropenia, in 11.1% of patients, leukopenia (8.9%), and thrombocytopenia (6.7%). There were no grade 4 adverse events.
The study was sponsored by Biotech Pharmaceutical. Dr. Qin has disclosed no relevant financial relationships. Dr. Eng has disclosed relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer. Dr. Gralow has disclosed relationships with Genentech, AstraZeneca, Hexal, Puma Biotechnology, Roche, Novartis, Seagen, and Genomic Health.
A version of this article first appeared on Medscape.com.
FROM ASCO 2022
Adagrasib shows durable benefit in KRAS-mutated NSCLC
with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.
“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.
“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.
New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.
Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.
If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.
Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
Published clinical data
The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.
It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.
Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.
On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.
Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.
Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.
“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.
Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
CNS metastases
At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.
As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.
The study was funded by Mirati Therapeutics.
A version of this article first appeared on Medscape.com.
with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.
“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.
“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.
New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.
Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.
If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.
Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
Published clinical data
The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.
It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.
Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.
On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.
Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.
Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.
“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.
Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
CNS metastases
At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.
As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.
The study was funded by Mirati Therapeutics.
A version of this article first appeared on Medscape.com.
with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.
“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.
“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.
New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.
Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.
If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.
Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
Published clinical data
The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.
It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.
Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.
On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.
Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.
Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.
“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.
Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
CNS metastases
At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.
As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.
The study was funded by Mirati Therapeutics.
A version of this article first appeared on Medscape.com.
FROM ASCO 2022
ctDNA identifies patients with colon cancer who can skip chemo
and also identifies those who are unlikely to benefit, allowing them to skip that treatment.
The results are from the phase 2 DYNAMIC trial.
“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.
The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.
The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.
Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.
The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.
The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.
“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.
“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.
They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
Study details
For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.
The Safe-SeqS tumor-informed personalized ctDNA assay was used to detect ctDNA in the experimental group. Patients with a ctDNA-positive result at 4 or 7 weeks after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy; those who were ctDNA-negative were observed during follow-up.
Fewer patients overall in the ctDNA-guided group, compared with the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).
Two-year recurrence-free survival (RFS) in the ctDNA-guided treatment group was noninferior to that in the standard management group (93.5% vs. 92.4%). Three-year RFS was 86.4% in ctDNA-positive patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in a clinical low-risk subgroup.
ASCO expert Cathy Eng, MD, applauded the findings, stating in a press release that “thanks to the results of this study, we may now be able to use it to better identify which patient with stage 2 colon cancer would benefit from post surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival.”
Dr. Eng is the David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, co-director of GI oncology, and professor of medicine in hematology and oncology at Vanderbilt University, Nashville, Tenn.
Next steps
The authors note that a randomized trial is being considered in which ctDNA-positive and -negative patients would be randomized to treatment versus no treatment. This could provide more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets, according to the press release.
The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, U.S. National Institutes of Health, the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, and Eastern Health Research Foundation. Dr. Tie has reported receiving honoraria from Inivata and Servier and serving as a consultant or advisor for AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, and Pierre Fabre.
A version of this article first appeared on Medscape.com.
and also identifies those who are unlikely to benefit, allowing them to skip that treatment.
The results are from the phase 2 DYNAMIC trial.
“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.
The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.
The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.
Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.
The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.
The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.
“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.
“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.
They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
Study details
For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.
The Safe-SeqS tumor-informed personalized ctDNA assay was used to detect ctDNA in the experimental group. Patients with a ctDNA-positive result at 4 or 7 weeks after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy; those who were ctDNA-negative were observed during follow-up.
Fewer patients overall in the ctDNA-guided group, compared with the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).
Two-year recurrence-free survival (RFS) in the ctDNA-guided treatment group was noninferior to that in the standard management group (93.5% vs. 92.4%). Three-year RFS was 86.4% in ctDNA-positive patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in a clinical low-risk subgroup.
ASCO expert Cathy Eng, MD, applauded the findings, stating in a press release that “thanks to the results of this study, we may now be able to use it to better identify which patient with stage 2 colon cancer would benefit from post surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival.”
Dr. Eng is the David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, co-director of GI oncology, and professor of medicine in hematology and oncology at Vanderbilt University, Nashville, Tenn.
Next steps
The authors note that a randomized trial is being considered in which ctDNA-positive and -negative patients would be randomized to treatment versus no treatment. This could provide more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets, according to the press release.
The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, U.S. National Institutes of Health, the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, and Eastern Health Research Foundation. Dr. Tie has reported receiving honoraria from Inivata and Servier and serving as a consultant or advisor for AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, and Pierre Fabre.
A version of this article first appeared on Medscape.com.
and also identifies those who are unlikely to benefit, allowing them to skip that treatment.
The results are from the phase 2 DYNAMIC trial.
“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.
The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.
The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.
Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.
The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.
The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.
“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.
“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.
They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
Study details
For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.
The Safe-SeqS tumor-informed personalized ctDNA assay was used to detect ctDNA in the experimental group. Patients with a ctDNA-positive result at 4 or 7 weeks after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy; those who were ctDNA-negative were observed during follow-up.
Fewer patients overall in the ctDNA-guided group, compared with the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).
Two-year recurrence-free survival (RFS) in the ctDNA-guided treatment group was noninferior to that in the standard management group (93.5% vs. 92.4%). Three-year RFS was 86.4% in ctDNA-positive patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in a clinical low-risk subgroup.
ASCO expert Cathy Eng, MD, applauded the findings, stating in a press release that “thanks to the results of this study, we may now be able to use it to better identify which patient with stage 2 colon cancer would benefit from post surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival.”
Dr. Eng is the David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, co-director of GI oncology, and professor of medicine in hematology and oncology at Vanderbilt University, Nashville, Tenn.
Next steps
The authors note that a randomized trial is being considered in which ctDNA-positive and -negative patients would be randomized to treatment versus no treatment. This could provide more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets, according to the press release.
The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, U.S. National Institutes of Health, the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, and Eastern Health Research Foundation. Dr. Tie has reported receiving honoraria from Inivata and Servier and serving as a consultant or advisor for AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, and Pierre Fabre.
A version of this article first appeared on Medscape.com.
AT ASCO 2022
Oncologists flock to Chicago for ASCO, after 2 years online
And it appears many are eager to attend the American Society of Clinical Oncology annual meeting in person now that they can.
By early May, ASCO already had 30,000 registrations, of which 80% were in person – there were 27,000 hotel reservations.
“That’s almost identical to where we were in terms of numbers in 2019 at the same point in time,” Julie Gralow, MD, chief medical officer at ASCO, said in an interview.
These figures, which are from May 11, are likely to increase. In past years, there has been an upswing in registrations right before the meeting starts.
The annual meeting begins on Friday, June 3, and runs until Tuesday, June 7. It will be held in Chicago, yet again, in the vast McCormick Place, sections of which were transformed into field hospital wards when the pandemic hit in 2020.
But the meeting will also continue to be transmitted virtually, as it has been for the past 2 years, for those not attending in person.
“I do think that the hybrid model will move forward,” Dr. Gralow said. “We can get a lot of attendees, especially from very distant places, who can’t travel, or can’t easily travel, and we have learned how to make that experience better for them as well.”
Attendees can also change their minds if, for example, rising numbers of COVID cases as the meeting nears put them off traveling. “We are allowing people to change to virtual. So I think there may be a little bit of that, depending on what happens to COVID in different parts of the world,” Dr. Gralow commented.
For those who do attend, the organization is “doing the best that we can to keep people safe,” said Dr. Gralow, who was previously a professor of global health and is now a breast medical oncologist and clinical trialist.
To attend in person, ASCO is mandating proof of vaccination (which in the United States means two doses of the COVID vaccine). “If you prove in advance that you are vaccinated, we will send you your badge, so you don’t have to stand in line,” she added.
“As far as masks go, we are saying right now that we are complying with Chicago’s rules, which mean there is no mandatory indoor masking,” she continued. “We are recommending masking because this is a group of physicians who treat immunocompromised patients. So we are recommending that.”
This stance has gotten some push-back on Twitter from both physicians and patient advocates, with some surprised that masking is not mandatory.
“I know that ‘mask-optional’ meetings mean most will omit masks; I literally just saw this at my last meeting as one of the few masked MDs,” commented radiation oncologist Fumiko Ladd Chino, MD. She appealed to the organizers with a plea: “There’s still time to change #ASCO22 policies. We’re in it for patient health.”
Patient advocate Manju George, MVSc, PhD, a rectal cancer survivor, was also campaigning for a change in policy by setting up a letter that others could sign, adding that “ASCO leadership is being flooded with pleads from concerned HCPs.”
When asked whether it was considering a change in mask policy, ASCO replied: “As far as health and safety go, the protocols we’ve put in place meet or exceed current [World Health Organization, [Centers for Disease Control and Prevention, and city of Chicago guidelines. ASCO is also closely coordinating with both the city and the convention center and we are actively monitoring local conditions.”
“To protect the health and safety of all meeting attendees, our protocols require attendees to be fully vaccinated and self-test negative for COVID-19 within 48 hours prior to their arrival at the meeting. In addition, we expect all attendees to be masked when indoors and are encouraging regular self-testing. We fully expect members of our community to do their part to help keep everyone safe, and we’re making it easy for attendees to comply with our policies by providing medical-grade masks as well as both rapid antigen and [polymerase chain reaction] COVID-19 tests,” the organization said.
There will also be a notification system so attendees can select how they identify for closeness, with red meaning stand back, no hugs, no handshakes; yellow signifying something more intermediate; and green signaling the person is okay with contact with a handshake or a hug. This system has already been used during smaller ASCO subspecialty meetings earlier this year, and feedback from delegates was positive, Dr. Gralow commented.
Advancing equitable care
The theme of the 2022 meeting, chosen by ASCO President Everett Vokes, MD, is advancing equitable cancer care through innovation.
It builds on the theme of equity from 2021, chosen by previous president Lori Pierce, MD, which was “Equity: Every Patient. Every Day. Everywhere.”
Some of this relates to disparities in equity, commented Dr. Gralow. This is the focus of a premeeting press briefing on May 26 that will highlight a few abstracts that focus on disparities and what can be done to address them. One study (abstract 6511) focuses on telemedicine, which was increasingly used during the pandemic, but the results show not all U.S. patient populations could access the specialty care they needed in this way.
De-escalation of therapy
De-escalation of therapy is another theme running through the meeting.
“There are some cancers where we have achieved such good outcomes that it is time to look at de-escalating therapy because we know that we are probably way overtreating a component of those patients. ... So we are looking at whether we can find subpopulations where we can back off on therapy,” commented Dr. Gralow.
One example is the LUMINA trial in breast cancer (abstract LBA501), which looked at omitting radiotherapy after surgery. “In standard practice we have already been doing this, not based on solid data, but based on an accumulation of retrospective analyses and similar evidence,” commented Dr. Gralow. This trial tested the approach prospectively, lowered the age range of patients, and better defined which patients were likely to benefit.
Another example is the DYNAMIC trial in colorectal cancer (abstract LBA-100), which looks at omitting chemotherapy based on levels of circulating tumor DNA after surgery. These patients had stage 2 disease and generally do very well with surgery and adjuvant chemotherapy, Dr. Gralow stated. This trial aims to find the subset of patients who could do just as well without the chemotherapy; it may also identify those patients at the other end of the scale, who perhaps need a bit more treatment, she added.
Spotlight on innovation
The focus on innovation includes exploring drugs developed outside the United States. One example is nimotuzumab, which is already approved in China for use in nasopharyngeal cancer but is also being explored in other cancer types. At ASCO, data will be presented in patients with KRAS wild-type pancreatic cancer (abstract 4011). This study, like the other trials with nimotuzumab, was conducted in China.
This brings up an important point about the data the Food and Drug Administration requires for new drug approvals, commented Dr. Gralow.
She noted that the FDA recently rejected an application for sintilimab, a drug also developed in China, on the basis that all trial data submitted for approval were from China. The agency said it would like to see multiregional clinical trials and trials that reflect the U.S. cancer population.
Advice for attendees
A large trial in a rare cancer promises to establish a new standard of care, where previously a number of different regimens have been used in various parts of the world, and even at different hospitals within the same country. These are the results from an international trial in children and adolescents/young adults with Ewing’s sarcoma (abstract LBA-02). “I have been told by experts in the field that these results will change practice ... [and] will have a global impact,” commented Dr. Gralow.
In addition to the scientific sessions that will see new data, there are a number of educational sessions that will tackle tricky issues that clinicians sometimes face. “Microaggressions, Bias, and Equity in the Workplace” will be discussed in one session, while another promises, “Strategies to Address Moral Distress in Clinicians: What Should We Do When We Don’t Know What to Do?”
There is also a special session featuring the “Cancer Groundshot: Addressing the Global and National Inequities in Cancer Care.” This is a move spearheaded by Bishal Gyawali, MD, PhD, from Brigham and Women’s Hospital, Boston, who was reacting to the lofty goals of the presidential Cancer Moonshot, including the aim of “ending cancer as we know it.” In a blog post in 2016 he suggested “forget the moon; let’s get back to blood and flesh reality on the ground ... [and] research that can be immediately applied to every global community.” He recounts the journey from ‘Blog Post to ASCO Session’ in a recent commentary.
Dr. Gyawali also has some advice for those attending the ASCO annual meeting: Reach out to people you respect, trust that connections will happen, scrutinize the data, listen critically for jargon, and perhaps most importantly, have fun.
“There’s more to life than your job,” he wrote. “Don’t stress. Think about the bigger picture. Think about your patients. And remember, life is beautiful, even when it feels like it isn’t.”
A version of this article first appeared on Medscape.com.
And it appears many are eager to attend the American Society of Clinical Oncology annual meeting in person now that they can.
By early May, ASCO already had 30,000 registrations, of which 80% were in person – there were 27,000 hotel reservations.
“That’s almost identical to where we were in terms of numbers in 2019 at the same point in time,” Julie Gralow, MD, chief medical officer at ASCO, said in an interview.
These figures, which are from May 11, are likely to increase. In past years, there has been an upswing in registrations right before the meeting starts.
The annual meeting begins on Friday, June 3, and runs until Tuesday, June 7. It will be held in Chicago, yet again, in the vast McCormick Place, sections of which were transformed into field hospital wards when the pandemic hit in 2020.
But the meeting will also continue to be transmitted virtually, as it has been for the past 2 years, for those not attending in person.
“I do think that the hybrid model will move forward,” Dr. Gralow said. “We can get a lot of attendees, especially from very distant places, who can’t travel, or can’t easily travel, and we have learned how to make that experience better for them as well.”
Attendees can also change their minds if, for example, rising numbers of COVID cases as the meeting nears put them off traveling. “We are allowing people to change to virtual. So I think there may be a little bit of that, depending on what happens to COVID in different parts of the world,” Dr. Gralow commented.
For those who do attend, the organization is “doing the best that we can to keep people safe,” said Dr. Gralow, who was previously a professor of global health and is now a breast medical oncologist and clinical trialist.
To attend in person, ASCO is mandating proof of vaccination (which in the United States means two doses of the COVID vaccine). “If you prove in advance that you are vaccinated, we will send you your badge, so you don’t have to stand in line,” she added.
“As far as masks go, we are saying right now that we are complying with Chicago’s rules, which mean there is no mandatory indoor masking,” she continued. “We are recommending masking because this is a group of physicians who treat immunocompromised patients. So we are recommending that.”
This stance has gotten some push-back on Twitter from both physicians and patient advocates, with some surprised that masking is not mandatory.
“I know that ‘mask-optional’ meetings mean most will omit masks; I literally just saw this at my last meeting as one of the few masked MDs,” commented radiation oncologist Fumiko Ladd Chino, MD. She appealed to the organizers with a plea: “There’s still time to change #ASCO22 policies. We’re in it for patient health.”
Patient advocate Manju George, MVSc, PhD, a rectal cancer survivor, was also campaigning for a change in policy by setting up a letter that others could sign, adding that “ASCO leadership is being flooded with pleads from concerned HCPs.”
When asked whether it was considering a change in mask policy, ASCO replied: “As far as health and safety go, the protocols we’ve put in place meet or exceed current [World Health Organization, [Centers for Disease Control and Prevention, and city of Chicago guidelines. ASCO is also closely coordinating with both the city and the convention center and we are actively monitoring local conditions.”
“To protect the health and safety of all meeting attendees, our protocols require attendees to be fully vaccinated and self-test negative for COVID-19 within 48 hours prior to their arrival at the meeting. In addition, we expect all attendees to be masked when indoors and are encouraging regular self-testing. We fully expect members of our community to do their part to help keep everyone safe, and we’re making it easy for attendees to comply with our policies by providing medical-grade masks as well as both rapid antigen and [polymerase chain reaction] COVID-19 tests,” the organization said.
There will also be a notification system so attendees can select how they identify for closeness, with red meaning stand back, no hugs, no handshakes; yellow signifying something more intermediate; and green signaling the person is okay with contact with a handshake or a hug. This system has already been used during smaller ASCO subspecialty meetings earlier this year, and feedback from delegates was positive, Dr. Gralow commented.
Advancing equitable care
The theme of the 2022 meeting, chosen by ASCO President Everett Vokes, MD, is advancing equitable cancer care through innovation.
It builds on the theme of equity from 2021, chosen by previous president Lori Pierce, MD, which was “Equity: Every Patient. Every Day. Everywhere.”
Some of this relates to disparities in equity, commented Dr. Gralow. This is the focus of a premeeting press briefing on May 26 that will highlight a few abstracts that focus on disparities and what can be done to address them. One study (abstract 6511) focuses on telemedicine, which was increasingly used during the pandemic, but the results show not all U.S. patient populations could access the specialty care they needed in this way.
De-escalation of therapy
De-escalation of therapy is another theme running through the meeting.
“There are some cancers where we have achieved such good outcomes that it is time to look at de-escalating therapy because we know that we are probably way overtreating a component of those patients. ... So we are looking at whether we can find subpopulations where we can back off on therapy,” commented Dr. Gralow.
One example is the LUMINA trial in breast cancer (abstract LBA501), which looked at omitting radiotherapy after surgery. “In standard practice we have already been doing this, not based on solid data, but based on an accumulation of retrospective analyses and similar evidence,” commented Dr. Gralow. This trial tested the approach prospectively, lowered the age range of patients, and better defined which patients were likely to benefit.
Another example is the DYNAMIC trial in colorectal cancer (abstract LBA-100), which looks at omitting chemotherapy based on levels of circulating tumor DNA after surgery. These patients had stage 2 disease and generally do very well with surgery and adjuvant chemotherapy, Dr. Gralow stated. This trial aims to find the subset of patients who could do just as well without the chemotherapy; it may also identify those patients at the other end of the scale, who perhaps need a bit more treatment, she added.
Spotlight on innovation
The focus on innovation includes exploring drugs developed outside the United States. One example is nimotuzumab, which is already approved in China for use in nasopharyngeal cancer but is also being explored in other cancer types. At ASCO, data will be presented in patients with KRAS wild-type pancreatic cancer (abstract 4011). This study, like the other trials with nimotuzumab, was conducted in China.
This brings up an important point about the data the Food and Drug Administration requires for new drug approvals, commented Dr. Gralow.
She noted that the FDA recently rejected an application for sintilimab, a drug also developed in China, on the basis that all trial data submitted for approval were from China. The agency said it would like to see multiregional clinical trials and trials that reflect the U.S. cancer population.
Advice for attendees
A large trial in a rare cancer promises to establish a new standard of care, where previously a number of different regimens have been used in various parts of the world, and even at different hospitals within the same country. These are the results from an international trial in children and adolescents/young adults with Ewing’s sarcoma (abstract LBA-02). “I have been told by experts in the field that these results will change practice ... [and] will have a global impact,” commented Dr. Gralow.
In addition to the scientific sessions that will see new data, there are a number of educational sessions that will tackle tricky issues that clinicians sometimes face. “Microaggressions, Bias, and Equity in the Workplace” will be discussed in one session, while another promises, “Strategies to Address Moral Distress in Clinicians: What Should We Do When We Don’t Know What to Do?”
There is also a special session featuring the “Cancer Groundshot: Addressing the Global and National Inequities in Cancer Care.” This is a move spearheaded by Bishal Gyawali, MD, PhD, from Brigham and Women’s Hospital, Boston, who was reacting to the lofty goals of the presidential Cancer Moonshot, including the aim of “ending cancer as we know it.” In a blog post in 2016 he suggested “forget the moon; let’s get back to blood and flesh reality on the ground ... [and] research that can be immediately applied to every global community.” He recounts the journey from ‘Blog Post to ASCO Session’ in a recent commentary.
Dr. Gyawali also has some advice for those attending the ASCO annual meeting: Reach out to people you respect, trust that connections will happen, scrutinize the data, listen critically for jargon, and perhaps most importantly, have fun.
“There’s more to life than your job,” he wrote. “Don’t stress. Think about the bigger picture. Think about your patients. And remember, life is beautiful, even when it feels like it isn’t.”
A version of this article first appeared on Medscape.com.
And it appears many are eager to attend the American Society of Clinical Oncology annual meeting in person now that they can.
By early May, ASCO already had 30,000 registrations, of which 80% were in person – there were 27,000 hotel reservations.
“That’s almost identical to where we were in terms of numbers in 2019 at the same point in time,” Julie Gralow, MD, chief medical officer at ASCO, said in an interview.
These figures, which are from May 11, are likely to increase. In past years, there has been an upswing in registrations right before the meeting starts.
The annual meeting begins on Friday, June 3, and runs until Tuesday, June 7. It will be held in Chicago, yet again, in the vast McCormick Place, sections of which were transformed into field hospital wards when the pandemic hit in 2020.
But the meeting will also continue to be transmitted virtually, as it has been for the past 2 years, for those not attending in person.
“I do think that the hybrid model will move forward,” Dr. Gralow said. “We can get a lot of attendees, especially from very distant places, who can’t travel, or can’t easily travel, and we have learned how to make that experience better for them as well.”
Attendees can also change their minds if, for example, rising numbers of COVID cases as the meeting nears put them off traveling. “We are allowing people to change to virtual. So I think there may be a little bit of that, depending on what happens to COVID in different parts of the world,” Dr. Gralow commented.
For those who do attend, the organization is “doing the best that we can to keep people safe,” said Dr. Gralow, who was previously a professor of global health and is now a breast medical oncologist and clinical trialist.
To attend in person, ASCO is mandating proof of vaccination (which in the United States means two doses of the COVID vaccine). “If you prove in advance that you are vaccinated, we will send you your badge, so you don’t have to stand in line,” she added.
“As far as masks go, we are saying right now that we are complying with Chicago’s rules, which mean there is no mandatory indoor masking,” she continued. “We are recommending masking because this is a group of physicians who treat immunocompromised patients. So we are recommending that.”
This stance has gotten some push-back on Twitter from both physicians and patient advocates, with some surprised that masking is not mandatory.
“I know that ‘mask-optional’ meetings mean most will omit masks; I literally just saw this at my last meeting as one of the few masked MDs,” commented radiation oncologist Fumiko Ladd Chino, MD. She appealed to the organizers with a plea: “There’s still time to change #ASCO22 policies. We’re in it for patient health.”
Patient advocate Manju George, MVSc, PhD, a rectal cancer survivor, was also campaigning for a change in policy by setting up a letter that others could sign, adding that “ASCO leadership is being flooded with pleads from concerned HCPs.”
When asked whether it was considering a change in mask policy, ASCO replied: “As far as health and safety go, the protocols we’ve put in place meet or exceed current [World Health Organization, [Centers for Disease Control and Prevention, and city of Chicago guidelines. ASCO is also closely coordinating with both the city and the convention center and we are actively monitoring local conditions.”
“To protect the health and safety of all meeting attendees, our protocols require attendees to be fully vaccinated and self-test negative for COVID-19 within 48 hours prior to their arrival at the meeting. In addition, we expect all attendees to be masked when indoors and are encouraging regular self-testing. We fully expect members of our community to do their part to help keep everyone safe, and we’re making it easy for attendees to comply with our policies by providing medical-grade masks as well as both rapid antigen and [polymerase chain reaction] COVID-19 tests,” the organization said.
There will also be a notification system so attendees can select how they identify for closeness, with red meaning stand back, no hugs, no handshakes; yellow signifying something more intermediate; and green signaling the person is okay with contact with a handshake or a hug. This system has already been used during smaller ASCO subspecialty meetings earlier this year, and feedback from delegates was positive, Dr. Gralow commented.
Advancing equitable care
The theme of the 2022 meeting, chosen by ASCO President Everett Vokes, MD, is advancing equitable cancer care through innovation.
It builds on the theme of equity from 2021, chosen by previous president Lori Pierce, MD, which was “Equity: Every Patient. Every Day. Everywhere.”
Some of this relates to disparities in equity, commented Dr. Gralow. This is the focus of a premeeting press briefing on May 26 that will highlight a few abstracts that focus on disparities and what can be done to address them. One study (abstract 6511) focuses on telemedicine, which was increasingly used during the pandemic, but the results show not all U.S. patient populations could access the specialty care they needed in this way.
De-escalation of therapy
De-escalation of therapy is another theme running through the meeting.
“There are some cancers where we have achieved such good outcomes that it is time to look at de-escalating therapy because we know that we are probably way overtreating a component of those patients. ... So we are looking at whether we can find subpopulations where we can back off on therapy,” commented Dr. Gralow.
One example is the LUMINA trial in breast cancer (abstract LBA501), which looked at omitting radiotherapy after surgery. “In standard practice we have already been doing this, not based on solid data, but based on an accumulation of retrospective analyses and similar evidence,” commented Dr. Gralow. This trial tested the approach prospectively, lowered the age range of patients, and better defined which patients were likely to benefit.
Another example is the DYNAMIC trial in colorectal cancer (abstract LBA-100), which looks at omitting chemotherapy based on levels of circulating tumor DNA after surgery. These patients had stage 2 disease and generally do very well with surgery and adjuvant chemotherapy, Dr. Gralow stated. This trial aims to find the subset of patients who could do just as well without the chemotherapy; it may also identify those patients at the other end of the scale, who perhaps need a bit more treatment, she added.
Spotlight on innovation
The focus on innovation includes exploring drugs developed outside the United States. One example is nimotuzumab, which is already approved in China for use in nasopharyngeal cancer but is also being explored in other cancer types. At ASCO, data will be presented in patients with KRAS wild-type pancreatic cancer (abstract 4011). This study, like the other trials with nimotuzumab, was conducted in China.
This brings up an important point about the data the Food and Drug Administration requires for new drug approvals, commented Dr. Gralow.
She noted that the FDA recently rejected an application for sintilimab, a drug also developed in China, on the basis that all trial data submitted for approval were from China. The agency said it would like to see multiregional clinical trials and trials that reflect the U.S. cancer population.
Advice for attendees
A large trial in a rare cancer promises to establish a new standard of care, where previously a number of different regimens have been used in various parts of the world, and even at different hospitals within the same country. These are the results from an international trial in children and adolescents/young adults with Ewing’s sarcoma (abstract LBA-02). “I have been told by experts in the field that these results will change practice ... [and] will have a global impact,” commented Dr. Gralow.
In addition to the scientific sessions that will see new data, there are a number of educational sessions that will tackle tricky issues that clinicians sometimes face. “Microaggressions, Bias, and Equity in the Workplace” will be discussed in one session, while another promises, “Strategies to Address Moral Distress in Clinicians: What Should We Do When We Don’t Know What to Do?”
There is also a special session featuring the “Cancer Groundshot: Addressing the Global and National Inequities in Cancer Care.” This is a move spearheaded by Bishal Gyawali, MD, PhD, from Brigham and Women’s Hospital, Boston, who was reacting to the lofty goals of the presidential Cancer Moonshot, including the aim of “ending cancer as we know it.” In a blog post in 2016 he suggested “forget the moon; let’s get back to blood and flesh reality on the ground ... [and] research that can be immediately applied to every global community.” He recounts the journey from ‘Blog Post to ASCO Session’ in a recent commentary.
Dr. Gyawali also has some advice for those attending the ASCO annual meeting: Reach out to people you respect, trust that connections will happen, scrutinize the data, listen critically for jargon, and perhaps most importantly, have fun.
“There’s more to life than your job,” he wrote. “Don’t stress. Think about the bigger picture. Think about your patients. And remember, life is beautiful, even when it feels like it isn’t.”
A version of this article first appeared on Medscape.com.