Patient & Survivor Care

TOPLINE:

For patients with early multinodular hepatocellular carcinoma (HCC) who are ineligible for liver transplant, liver resection provides a survival advantage over percutaneous radiofrequency ablation and transarterial chemoembolization (TACE).

METHODOLOGY:

• The presentation of HCC is often multinodular — meaning patients have two or three nodules measuring ≤ 3 cm each. Although liver resection is considered the gold standard curative treatment for early-stage disease, experts debate its efficacy in multinodular HCC, researchers explained.
• Using two large Italian registries with data from multiple centers, researchers compared the efficacy of liver resection, percutaneous radiofrequency ablation, and TACE in 720 patients with early multinodular HCC. Overall, 296 patients underwent liver resection, 240 had percutaneous radiofrequency ablation, and 184 underwent TACE.
• To avoid crossovers between groups, the researchers considered liver resection, percutaneous radiofrequency ablation, and TACE the main treatments in each population in a hierarchical order. That meant, in the liver resection group, researchers excluded patients undergoing a superior treatment during the follow-up, such as liver transplant. In the ablation group, patients undergoing surgery to treat HCC recurrences were excluded.
• The primary outcome was overall survival at 1, 3, and 5 years. The researchers used a matching-adjusted indirect comparison (MAIC) to balance data and control for confounding factors between the three treatment groups.

TAKEAWAY:

• After MAIC adjustment, the survival rate at 1 year was slightly lower in the liver resection group — 89% vs 94% in the ablation group and 91% in the TACE group. However, at 3 and 5 years, survival rates were better in the liver resection group — 71% at 3 years and 56% at 5 years vs 65% and 40%, respectively, in the ablation group and 49% and 29%, respectively, in the TACE group.
• Median overall survival was 69 months with liver resection, 54 months with ablation, and 34 months with TACE. Multivariable Cox survival analysis confirmed a significantly higher mortality risk with ablation (hazard ratio [HR], 1.41; P = .01) and TACE (HR, 1.86; P = .001) than with liver resection.
• In competing risk analyses, patients who underwent liver resection had a lower risk for HCC-related death than peers who had ablation (HR, 1.38; P = .07) or TACE (HR, 1.91; P = .006).
• In a subgroup survival analysis of patients with Child-Pugh class B cirrhosis, liver resection provided significantly better overall survival than TACE (HR, 2.79; P = .001) and higher overall survival than ablation (HR, 1.44; P = .21), but these findings were not statistically significant.

IN PRACTICE:

“The main result of the current study is the indisputable superiority” of liver resection over percutaneous radiofrequency ablation and TACE in patients with multinodular HCC, the researchers concluded. “For patients with early multinodular HCC who are ineligible for transplant, LR [liver resection] should be prioritized as the primary therapeutic option,” followed by percutaneous radiofrequency ablation and TACE, when resection is not feasible.

The authors of an invited commentary said the analysis provides “convincing” data that liver resection leads to superior 3- and 5-year survival. “All of our local therapies are getting better. Making each available under different clinical circumstances and combining these when appropriate provides patients with the best chance at cure with the least invasiveness,” the editorialists added.
 

SOURCE:

The study, with first author Alessandro Vitale, MD, PhD, with the Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy, and the accompanying commentary were published online last month in JAMA Surgery.

LIMITATIONS:

Selection bias cannot be ruled out due to potential hidden variables that were not collected in the centers’ databases. Not all patients included in the study were potentially treatable with all three proposed approaches. The study population was derived from Italian centers, which may have limited the generalizability of the results.

DISCLOSURES:

The study reported no specific funding. The authors reported various disclosures during the conduct of the study, including ties to AstraZeneca, AbbVie, Bayer, MSD, Roche, and Eisai. An editorialist reported ties to Medtronic, Theromics, Vergent Bioscience, Imugene, Sovato Health, XDemics, and Imugene.

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

TOPLINE:

For patients with early multinodular hepatocellular carcinoma (HCC) who are ineligible for liver transplant, liver resection provides a survival advantage over percutaneous radiofrequency ablation and transarterial chemoembolization (TACE).

METHODOLOGY:

• The presentation of HCC is often multinodular — meaning patients have two or three nodules measuring ≤ 3 cm each. Although liver resection is considered the gold standard curative treatment for early-stage disease, experts debate its efficacy in multinodular HCC, researchers explained.
• Using two large Italian registries with data from multiple centers, researchers compared the efficacy of liver resection, percutaneous radiofrequency ablation, and TACE in 720 patients with early multinodular HCC. Overall, 296 patients underwent liver resection, 240 had percutaneous radiofrequency ablation, and 184 underwent TACE.
• To avoid crossovers between groups, the researchers considered liver resection, percutaneous radiofrequency ablation, and TACE the main treatments in each population in a hierarchical order. That meant, in the liver resection group, researchers excluded patients undergoing a superior treatment during the follow-up, such as liver transplant. In the ablation group, patients undergoing surgery to treat HCC recurrences were excluded.
• The primary outcome was overall survival at 1, 3, and 5 years. The researchers used a matching-adjusted indirect comparison (MAIC) to balance data and control for confounding factors between the three treatment groups.

TAKEAWAY:

• After MAIC adjustment, the survival rate at 1 year was slightly lower in the liver resection group — 89% vs 94% in the ablation group and 91% in the TACE group. However, at 3 and 5 years, survival rates were better in the liver resection group — 71% at 3 years and 56% at 5 years vs 65% and 40%, respectively, in the ablation group and 49% and 29%, respectively, in the TACE group.
• Median overall survival was 69 months with liver resection, 54 months with ablation, and 34 months with TACE. Multivariable Cox survival analysis confirmed a significantly higher mortality risk with ablation (hazard ratio [HR], 1.41; P = .01) and TACE (HR, 1.86; P = .001) than with liver resection.
• In competing risk analyses, patients who underwent liver resection had a lower risk for HCC-related death than peers who had ablation (HR, 1.38; P = .07) or TACE (HR, 1.91; P = .006).
• In a subgroup survival analysis of patients with Child-Pugh class B cirrhosis, liver resection provided significantly better overall survival than TACE (HR, 2.79; P = .001) and higher overall survival than ablation (HR, 1.44; P = .21), but these findings were not statistically significant.

IN PRACTICE:

“The main result of the current study is the indisputable superiority” of liver resection over percutaneous radiofrequency ablation and TACE in patients with multinodular HCC, the researchers concluded. “For patients with early multinodular HCC who are ineligible for transplant, LR [liver resection] should be prioritized as the primary therapeutic option,” followed by percutaneous radiofrequency ablation and TACE, when resection is not feasible.

The authors of an invited commentary said the analysis provides “convincing” data that liver resection leads to superior 3- and 5-year survival. “All of our local therapies are getting better. Making each available under different clinical circumstances and combining these when appropriate provides patients with the best chance at cure with the least invasiveness,” the editorialists added.
 

SOURCE:

The study, with first author Alessandro Vitale, MD, PhD, with the Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy, and the accompanying commentary were published online last month in JAMA Surgery.

LIMITATIONS:

Selection bias cannot be ruled out due to potential hidden variables that were not collected in the centers’ databases. Not all patients included in the study were potentially treatable with all three proposed approaches. The study population was derived from Italian centers, which may have limited the generalizability of the results.

DISCLOSURES:

The study reported no specific funding. The authors reported various disclosures during the conduct of the study, including ties to AstraZeneca, AbbVie, Bayer, MSD, Roche, and Eisai. An editorialist reported ties to Medtronic, Theromics, Vergent Bioscience, Imugene, Sovato Health, XDemics, and Imugene.

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

TOPLINE:

For patients with early multinodular hepatocellular carcinoma (HCC) who are ineligible for liver transplant, liver resection provides a survival advantage over percutaneous radiofrequency ablation and transarterial chemoembolization (TACE).

METHODOLOGY:

• The presentation of HCC is often multinodular — meaning patients have two or three nodules measuring ≤ 3 cm each. Although liver resection is considered the gold standard curative treatment for early-stage disease, experts debate its efficacy in multinodular HCC, researchers explained.
• Using two large Italian registries with data from multiple centers, researchers compared the efficacy of liver resection, percutaneous radiofrequency ablation, and TACE in 720 patients with early multinodular HCC. Overall, 296 patients underwent liver resection, 240 had percutaneous radiofrequency ablation, and 184 underwent TACE.
• To avoid crossovers between groups, the researchers considered liver resection, percutaneous radiofrequency ablation, and TACE the main treatments in each population in a hierarchical order. That meant, in the liver resection group, researchers excluded patients undergoing a superior treatment during the follow-up, such as liver transplant. In the ablation group, patients undergoing surgery to treat HCC recurrences were excluded.
• The primary outcome was overall survival at 1, 3, and 5 years. The researchers used a matching-adjusted indirect comparison (MAIC) to balance data and control for confounding factors between the three treatment groups.

TAKEAWAY:

• After MAIC adjustment, the survival rate at 1 year was slightly lower in the liver resection group — 89% vs 94% in the ablation group and 91% in the TACE group. However, at 3 and 5 years, survival rates were better in the liver resection group — 71% at 3 years and 56% at 5 years vs 65% and 40%, respectively, in the ablation group and 49% and 29%, respectively, in the TACE group.
• Median overall survival was 69 months with liver resection, 54 months with ablation, and 34 months with TACE. Multivariable Cox survival analysis confirmed a significantly higher mortality risk with ablation (hazard ratio [HR], 1.41; P = .01) and TACE (HR, 1.86; P = .001) than with liver resection.
• In competing risk analyses, patients who underwent liver resection had a lower risk for HCC-related death than peers who had ablation (HR, 1.38; P = .07) or TACE (HR, 1.91; P = .006).
• In a subgroup survival analysis of patients with Child-Pugh class B cirrhosis, liver resection provided significantly better overall survival than TACE (HR, 2.79; P = .001) and higher overall survival than ablation (HR, 1.44; P = .21), but these findings were not statistically significant.

IN PRACTICE:

“The main result of the current study is the indisputable superiority” of liver resection over percutaneous radiofrequency ablation and TACE in patients with multinodular HCC, the researchers concluded. “For patients with early multinodular HCC who are ineligible for transplant, LR [liver resection] should be prioritized as the primary therapeutic option,” followed by percutaneous radiofrequency ablation and TACE, when resection is not feasible.

The authors of an invited commentary said the analysis provides “convincing” data that liver resection leads to superior 3- and 5-year survival. “All of our local therapies are getting better. Making each available under different clinical circumstances and combining these when appropriate provides patients with the best chance at cure with the least invasiveness,” the editorialists added.
 

SOURCE:

The study, with first author Alessandro Vitale, MD, PhD, with the Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy, and the accompanying commentary were published online last month in JAMA Surgery.

LIMITATIONS:

Selection bias cannot be ruled out due to potential hidden variables that were not collected in the centers’ databases. Not all patients included in the study were potentially treatable with all three proposed approaches. The study population was derived from Italian centers, which may have limited the generalizability of the results.

DISCLOSURES:

The study reported no specific funding. The authors reported various disclosures during the conduct of the study, including ties to AstraZeneca, AbbVie, Bayer, MSD, Roche, and Eisai. An editorialist reported ties to Medtronic, Theromics, Vergent Bioscience, Imugene, Sovato Health, XDemics, and Imugene.

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

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

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

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

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

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

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

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Association of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Association of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Association of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

The experimental drug inavolisib showed sustained benefit combined with standard treatment in advanced, PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) locally advanced metastatic breast cancer (LA/mBC), the INAVO120 trial.

The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.

The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).

“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.

In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
 

Methods and Results

The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.

At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.

In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.

Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.

There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.

Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
 

Rationale for Using PFS2 as Endpoint

The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.

“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.

“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”

The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.

The experimental drug inavolisib showed sustained benefit combined with standard treatment in advanced, PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) locally advanced metastatic breast cancer (LA/mBC), the INAVO120 trial.

The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.

The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).

“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.

In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
 

Methods and Results

The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.

At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.

In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.

Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.

There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.

Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
 

Rationale for Using PFS2 as Endpoint

The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.

“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.

“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”

The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.

The experimental drug inavolisib showed sustained benefit combined with standard treatment in advanced, PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) locally advanced metastatic breast cancer (LA/mBC), the INAVO120 trial.

The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.

The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).

“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.

In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
 

Methods and Results

The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.

At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.

In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.

Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.

There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.

Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
 

Rationale for Using PFS2 as Endpoint

The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.

“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.

“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”

The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.

CHICAGO — Carlos, a 21-year-old, lay in a hospital bed, barely clinging to life. Following a stem cell transplant for leukemia, Carlos had developed a life-threatening case of graft-vs-host disease.

But Carlos’ mother had faith.

“I have hope things will get better,” she said, via interpreter, to Richard Leiter, MD, a palliative care doctor in training at that time.

“I hope they will,” Dr. Leiter told her.

“I should have stopped there,” said Dr. Leiter, recounting an early-career lesson on hope during the ASCO Voices session at the American Society of Clinical Oncology annual meeting. “But in my eagerness to show my attending and myself that I could handle this conversation, I kept going, mistakenly.”

“But none of us think they will,” Dr. Leiter continued.

Carlos’ mother looked Dr. Leiter in the eye. “You want him to die,” she said.

“I knew, even then, that she was right,” recalled Dr. Leiter, now a palliative care physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, Boston.

Although there was nothing he could do to save Carlos, Dr. Leiter also couldn’t sit with the extreme suffering. “The pain was too great,” Dr. Leiter said. “I needed her to adopt our narrative that we had done everything we could to help him live, and now, we would do everything we could to help his death be a comfortable one.”

But looking back, Dr. Leiter realized, “How could we have asked her to accept what was fundamentally unacceptable, to comprehend the incomprehensible?”
 

The Importance of Hope

Hope is not only a feature of human cognition but also a measurable and malleable construct that can affect life outcomes, Alan B. Astrow, MD, said during an ASCO symposium on “The Art and Science of Hope.”

“How we think about hope directly influences patient care,” said Dr. Astrow, chief of hematology and medical oncology at NewYork-Presbyterian Brooklyn Methodist Hospital and a professor of clinical medicine at Weill Cornell Medicine in New York City.

Hope, whatever it turns out to be neurobiologically, is “very much a gift” that underlies human existence, he said.

Physicians have the capacity to restore or shatter a patient’s hopes, and those who come to understand the importance of hope will wish to extend the gift to others, Dr. Astrow said.

Asking patients about their hopes is the “golden question,” Steven Z. Pantilat, MD, said at the symposium. “When you think about the future, what do you hope for?”

Often, the answers reveal not only “things beyond a cure that matter tremendously to the patient but things that we can help with,” said Dr. Pantilat, professor and chief of the Division of Palliative Medicine at the University of California San Francisco.

Dr. Pantilat recalled a patient with advanced pancreatic cancer who wished to see her daughter’s wedding in 10 months. He knew that was unlikely, but the discussion led to another solution.

Her daughter moved the wedding to the ICU.

Hope can persist and uplift even in the darkest of times, and “as clinicians, we need to be in the true hope business,” he said.

While some patients may wish for a cure, others may want more time with family or comfort in the face of suffering. People can “hope for all the things that can still be, despite the fact that there’s a lot of things that can’t,” he said.

However, fear that a patient will hope for a cure, and that the difficult discussions to follow might destroy hope or lead to false hope, sometimes means physicians won’t begin the conversation.

“We want to be honest with our patients — compassionate and kind, but honest — when we talk about their hopes,” Dr. Pantilat explained. Sometimes that means he needs to tell patients, “I wish that could happen. I wish I had a treatment that could make your cancer go away, but unfortunately, I don’t. So let’s think about what else we can do to help you.”

Having these difficult discussions matters. The evidence, although limited, indicates that feeling hopeful can improve patients’ well-being and may even boost their cancer outcomes.

One recent study found, for instance, that patients who reported feeling more hopeful also had lower levels of depression and anxiety. Early research also suggests that greater levels of hope may have a hand in reducing inflammation in patients with ovarian cancer and could even improve survival in some patients with advanced cancer.

For Dr. Leiter, while these lessons came early in his career as a palliative care physician, they persist and influence his practice today.

“I know that I could not have prevented Carlos’ death. None of us could have, and none of us could have protected his mother from the unimaginable grief that will stay with her for the rest of her life,” he said. “But I could have made things just a little bit less difficult for her.

“I could have acted as her guide rather than her cross-examiner,” he continued, explaining that he now sees hope as “a generous collaborator” that can coexist with rising creatinine levels, failing livers, and fears about intubation.

“As clinicians, we can always find space to hope with our patients and their families,” he said. “So now, years later when I sit with a terrified and grieving family and they tell me they hope their loved one gets better, I remember Carlos’ mother’s eyes piercing mine ... and I know how to respond: ‘I hope so, too.’ And I do.”
 

A version of this article appeared on Medscape.com.

CHICAGO — Carlos, a 21-year-old, lay in a hospital bed, barely clinging to life. Following a stem cell transplant for leukemia, Carlos had developed a life-threatening case of graft-vs-host disease.

But Carlos’ mother had faith.

“I have hope things will get better,” she said, via interpreter, to Richard Leiter, MD, a palliative care doctor in training at that time.

“I hope they will,” Dr. Leiter told her.

“I should have stopped there,” said Dr. Leiter, recounting an early-career lesson on hope during the ASCO Voices session at the American Society of Clinical Oncology annual meeting. “But in my eagerness to show my attending and myself that I could handle this conversation, I kept going, mistakenly.”

“But none of us think they will,” Dr. Leiter continued.

Carlos’ mother looked Dr. Leiter in the eye. “You want him to die,” she said.

“I knew, even then, that she was right,” recalled Dr. Leiter, now a palliative care physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, Boston.

Although there was nothing he could do to save Carlos, Dr. Leiter also couldn’t sit with the extreme suffering. “The pain was too great,” Dr. Leiter said. “I needed her to adopt our narrative that we had done everything we could to help him live, and now, we would do everything we could to help his death be a comfortable one.”

But looking back, Dr. Leiter realized, “How could we have asked her to accept what was fundamentally unacceptable, to comprehend the incomprehensible?”
 

The Importance of Hope

Hope is not only a feature of human cognition but also a measurable and malleable construct that can affect life outcomes, Alan B. Astrow, MD, said during an ASCO symposium on “The Art and Science of Hope.”

“How we think about hope directly influences patient care,” said Dr. Astrow, chief of hematology and medical oncology at NewYork-Presbyterian Brooklyn Methodist Hospital and a professor of clinical medicine at Weill Cornell Medicine in New York City.

Hope, whatever it turns out to be neurobiologically, is “very much a gift” that underlies human existence, he said.

Physicians have the capacity to restore or shatter a patient’s hopes, and those who come to understand the importance of hope will wish to extend the gift to others, Dr. Astrow said.

Asking patients about their hopes is the “golden question,” Steven Z. Pantilat, MD, said at the symposium. “When you think about the future, what do you hope for?”

Often, the answers reveal not only “things beyond a cure that matter tremendously to the patient but things that we can help with,” said Dr. Pantilat, professor and chief of the Division of Palliative Medicine at the University of California San Francisco.

Dr. Pantilat recalled a patient with advanced pancreatic cancer who wished to see her daughter’s wedding in 10 months. He knew that was unlikely, but the discussion led to another solution.

Her daughter moved the wedding to the ICU.

Hope can persist and uplift even in the darkest of times, and “as clinicians, we need to be in the true hope business,” he said.

While some patients may wish for a cure, others may want more time with family or comfort in the face of suffering. People can “hope for all the things that can still be, despite the fact that there’s a lot of things that can’t,” he said.

However, fear that a patient will hope for a cure, and that the difficult discussions to follow might destroy hope or lead to false hope, sometimes means physicians won’t begin the conversation.

“We want to be honest with our patients — compassionate and kind, but honest — when we talk about their hopes,” Dr. Pantilat explained. Sometimes that means he needs to tell patients, “I wish that could happen. I wish I had a treatment that could make your cancer go away, but unfortunately, I don’t. So let’s think about what else we can do to help you.”

Having these difficult discussions matters. The evidence, although limited, indicates that feeling hopeful can improve patients’ well-being and may even boost their cancer outcomes.

One recent study found, for instance, that patients who reported feeling more hopeful also had lower levels of depression and anxiety. Early research also suggests that greater levels of hope may have a hand in reducing inflammation in patients with ovarian cancer and could even improve survival in some patients with advanced cancer.

For Dr. Leiter, while these lessons came early in his career as a palliative care physician, they persist and influence his practice today.

“I know that I could not have prevented Carlos’ death. None of us could have, and none of us could have protected his mother from the unimaginable grief that will stay with her for the rest of her life,” he said. “But I could have made things just a little bit less difficult for her.

“I could have acted as her guide rather than her cross-examiner,” he continued, explaining that he now sees hope as “a generous collaborator” that can coexist with rising creatinine levels, failing livers, and fears about intubation.

“As clinicians, we can always find space to hope with our patients and their families,” he said. “So now, years later when I sit with a terrified and grieving family and they tell me they hope their loved one gets better, I remember Carlos’ mother’s eyes piercing mine ... and I know how to respond: ‘I hope so, too.’ And I do.”
 

A version of this article appeared on Medscape.com.

CHICAGO — Carlos, a 21-year-old, lay in a hospital bed, barely clinging to life. Following a stem cell transplant for leukemia, Carlos had developed a life-threatening case of graft-vs-host disease.

But Carlos’ mother had faith.

“I have hope things will get better,” she said, via interpreter, to Richard Leiter, MD, a palliative care doctor in training at that time.

“I hope they will,” Dr. Leiter told her.

“I should have stopped there,” said Dr. Leiter, recounting an early-career lesson on hope during the ASCO Voices session at the American Society of Clinical Oncology annual meeting. “But in my eagerness to show my attending and myself that I could handle this conversation, I kept going, mistakenly.”

“But none of us think they will,” Dr. Leiter continued.

Carlos’ mother looked Dr. Leiter in the eye. “You want him to die,” she said.

“I knew, even then, that she was right,” recalled Dr. Leiter, now a palliative care physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, Boston.

Although there was nothing he could do to save Carlos, Dr. Leiter also couldn’t sit with the extreme suffering. “The pain was too great,” Dr. Leiter said. “I needed her to adopt our narrative that we had done everything we could to help him live, and now, we would do everything we could to help his death be a comfortable one.”

But looking back, Dr. Leiter realized, “How could we have asked her to accept what was fundamentally unacceptable, to comprehend the incomprehensible?”
 

The Importance of Hope

Hope is not only a feature of human cognition but also a measurable and malleable construct that can affect life outcomes, Alan B. Astrow, MD, said during an ASCO symposium on “The Art and Science of Hope.”

“How we think about hope directly influences patient care,” said Dr. Astrow, chief of hematology and medical oncology at NewYork-Presbyterian Brooklyn Methodist Hospital and a professor of clinical medicine at Weill Cornell Medicine in New York City.

Hope, whatever it turns out to be neurobiologically, is “very much a gift” that underlies human existence, he said.

Physicians have the capacity to restore or shatter a patient’s hopes, and those who come to understand the importance of hope will wish to extend the gift to others, Dr. Astrow said.

Asking patients about their hopes is the “golden question,” Steven Z. Pantilat, MD, said at the symposium. “When you think about the future, what do you hope for?”

Often, the answers reveal not only “things beyond a cure that matter tremendously to the patient but things that we can help with,” said Dr. Pantilat, professor and chief of the Division of Palliative Medicine at the University of California San Francisco.

Dr. Pantilat recalled a patient with advanced pancreatic cancer who wished to see her daughter’s wedding in 10 months. He knew that was unlikely, but the discussion led to another solution.

Her daughter moved the wedding to the ICU.

Hope can persist and uplift even in the darkest of times, and “as clinicians, we need to be in the true hope business,” he said.

While some patients may wish for a cure, others may want more time with family or comfort in the face of suffering. People can “hope for all the things that can still be, despite the fact that there’s a lot of things that can’t,” he said.

However, fear that a patient will hope for a cure, and that the difficult discussions to follow might destroy hope or lead to false hope, sometimes means physicians won’t begin the conversation.

“We want to be honest with our patients — compassionate and kind, but honest — when we talk about their hopes,” Dr. Pantilat explained. Sometimes that means he needs to tell patients, “I wish that could happen. I wish I had a treatment that could make your cancer go away, but unfortunately, I don’t. So let’s think about what else we can do to help you.”

Having these difficult discussions matters. The evidence, although limited, indicates that feeling hopeful can improve patients’ well-being and may even boost their cancer outcomes.

One recent study found, for instance, that patients who reported feeling more hopeful also had lower levels of depression and anxiety. Early research also suggests that greater levels of hope may have a hand in reducing inflammation in patients with ovarian cancer and could even improve survival in some patients with advanced cancer.

For Dr. Leiter, while these lessons came early in his career as a palliative care physician, they persist and influence his practice today.

“I know that I could not have prevented Carlos’ death. None of us could have, and none of us could have protected his mother from the unimaginable grief that will stay with her for the rest of her life,” he said. “But I could have made things just a little bit less difficult for her.

“I could have acted as her guide rather than her cross-examiner,” he continued, explaining that he now sees hope as “a generous collaborator” that can coexist with rising creatinine levels, failing livers, and fears about intubation.

“As clinicians, we can always find space to hope with our patients and their families,” he said. “So now, years later when I sit with a terrified and grieving family and they tell me they hope their loved one gets better, I remember Carlos’ mother’s eyes piercing mine ... and I know how to respond: ‘I hope so, too.’ And I do.”
 

A version of this article appeared on Medscape.com.

TOPLINE:

The artificial intelligence (AI) chatbot ChatGPT can significantly improve the readability of online cancer-related patient information while maintaining the content’s quality, a recent study found.

METHODOLOGY:

• Patients with cancer often search for cancer information online after their diagnosis, with most seeking information from their oncologists’ websites. However, the online materials often exceed the average reading level of the US population, limiting accessibility and comprehension.
• Researchers asked ChatGPT 4.0 to rewrite content about breast, colon, lung, prostate, and pancreas cancer, aiming for a sixth-grade readability level. The content came from a random sample of documents from 34 patient-facing websites associated with National Comprehensive Cancer Network (NCCN) member institutions.
• Readability, accuracy, similarity, and quality of the rewritten content were assessed using several established metrics and tools, including an F1 score, which assesses the precision and recall of a machine-learning model; a cosine similarity score, which measures similarities and is often used to detect plagiarism; and the DISCERN instrument, which helps assess the quality of the AI-rewritten information.
• The primary outcome was the mean readability score for the original and AI-generated content.

TAKEAWAY:

• The original content had an average readability level equivalent to a university freshman (grade 13). Following the AI revision, the readability level improved to a high school freshman level (grade 9).
• The rewritten content had high accuracy, with an overall F1 score of 0.87 (a good score is 0.8-0.9).
• The rewritten content had a high cosine similarity score of 0.915 (scores range from 0 to 1, with 0 indicating no similarity and 1 indicating complete similarity). Researchers attributed the improved readability to the use of simpler words and shorter sentences.
• Quality assessment using the DISCERN instrument showed that the AI-rewritten content maintained a “good” quality rating, similar to that of the original content.

IN PRACTICE:

Society has become increasingly dependent on online educational materials, and considering that more than half of Americans may not be literate beyond an eighth-grade level, our AI intervention offers a potential low-cost solution to narrow the gap between patient health literacy and content received from the nation’s leading cancer centers, the authors wrote.

SOURCE:

The study, with first author Andres A. Abreu, MD, with UT Southwestern Medical Center, Dallas, Texas, was published online in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The study was limited to English-language content from NCCN member websites, so the findings may not be generalizable to other sources or languages. Readability alone cannot guarantee comprehension. Factors such as material design and audiovisual aids were not evaluated.

DISCLOSURES:

The study did not report a funding source. The authors reported several disclosures but none related to the study. Herbert J. Zeh disclosed serving as a scientific advisor for Surgical Safety Technologies; Dr. Polanco disclosed serving as a consultant for Iota Biosciences and Palisade Bio and as a proctor for Intuitive Surgical.

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

TOPLINE:

The artificial intelligence (AI) chatbot ChatGPT can significantly improve the readability of online cancer-related patient information while maintaining the content’s quality, a recent study found.

METHODOLOGY:

• Patients with cancer often search for cancer information online after their diagnosis, with most seeking information from their oncologists’ websites. However, the online materials often exceed the average reading level of the US population, limiting accessibility and comprehension.
• Researchers asked ChatGPT 4.0 to rewrite content about breast, colon, lung, prostate, and pancreas cancer, aiming for a sixth-grade readability level. The content came from a random sample of documents from 34 patient-facing websites associated with National Comprehensive Cancer Network (NCCN) member institutions.
• Readability, accuracy, similarity, and quality of the rewritten content were assessed using several established metrics and tools, including an F1 score, which assesses the precision and recall of a machine-learning model; a cosine similarity score, which measures similarities and is often used to detect plagiarism; and the DISCERN instrument, which helps assess the quality of the AI-rewritten information.
• The primary outcome was the mean readability score for the original and AI-generated content.

TAKEAWAY:

• The original content had an average readability level equivalent to a university freshman (grade 13). Following the AI revision, the readability level improved to a high school freshman level (grade 9).
• The rewritten content had high accuracy, with an overall F1 score of 0.87 (a good score is 0.8-0.9).
• The rewritten content had a high cosine similarity score of 0.915 (scores range from 0 to 1, with 0 indicating no similarity and 1 indicating complete similarity). Researchers attributed the improved readability to the use of simpler words and shorter sentences.
• Quality assessment using the DISCERN instrument showed that the AI-rewritten content maintained a “good” quality rating, similar to that of the original content.

IN PRACTICE:

Society has become increasingly dependent on online educational materials, and considering that more than half of Americans may not be literate beyond an eighth-grade level, our AI intervention offers a potential low-cost solution to narrow the gap between patient health literacy and content received from the nation’s leading cancer centers, the authors wrote.

SOURCE:

The study, with first author Andres A. Abreu, MD, with UT Southwestern Medical Center, Dallas, Texas, was published online in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The study was limited to English-language content from NCCN member websites, so the findings may not be generalizable to other sources or languages. Readability alone cannot guarantee comprehension. Factors such as material design and audiovisual aids were not evaluated.

DISCLOSURES:

The study did not report a funding source. The authors reported several disclosures but none related to the study. Herbert J. Zeh disclosed serving as a scientific advisor for Surgical Safety Technologies; Dr. Polanco disclosed serving as a consultant for Iota Biosciences and Palisade Bio and as a proctor for Intuitive Surgical.

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

TOPLINE:

The artificial intelligence (AI) chatbot ChatGPT can significantly improve the readability of online cancer-related patient information while maintaining the content’s quality, a recent study found.

METHODOLOGY:

• Patients with cancer often search for cancer information online after their diagnosis, with most seeking information from their oncologists’ websites. However, the online materials often exceed the average reading level of the US population, limiting accessibility and comprehension.
• Researchers asked ChatGPT 4.0 to rewrite content about breast, colon, lung, prostate, and pancreas cancer, aiming for a sixth-grade readability level. The content came from a random sample of documents from 34 patient-facing websites associated with National Comprehensive Cancer Network (NCCN) member institutions.
• Readability, accuracy, similarity, and quality of the rewritten content were assessed using several established metrics and tools, including an F1 score, which assesses the precision and recall of a machine-learning model; a cosine similarity score, which measures similarities and is often used to detect plagiarism; and the DISCERN instrument, which helps assess the quality of the AI-rewritten information.
• The primary outcome was the mean readability score for the original and AI-generated content.

TAKEAWAY:

• The original content had an average readability level equivalent to a university freshman (grade 13). Following the AI revision, the readability level improved to a high school freshman level (grade 9).
• The rewritten content had high accuracy, with an overall F1 score of 0.87 (a good score is 0.8-0.9).
• The rewritten content had a high cosine similarity score of 0.915 (scores range from 0 to 1, with 0 indicating no similarity and 1 indicating complete similarity). Researchers attributed the improved readability to the use of simpler words and shorter sentences.
• Quality assessment using the DISCERN instrument showed that the AI-rewritten content maintained a “good” quality rating, similar to that of the original content.

IN PRACTICE:

Society has become increasingly dependent on online educational materials, and considering that more than half of Americans may not be literate beyond an eighth-grade level, our AI intervention offers a potential low-cost solution to narrow the gap between patient health literacy and content received from the nation’s leading cancer centers, the authors wrote.

SOURCE:

The study, with first author Andres A. Abreu, MD, with UT Southwestern Medical Center, Dallas, Texas, was published online in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The study was limited to English-language content from NCCN member websites, so the findings may not be generalizable to other sources or languages. Readability alone cannot guarantee comprehension. Factors such as material design and audiovisual aids were not evaluated.

DISCLOSURES:

The study did not report a funding source. The authors reported several disclosures but none related to the study. Herbert J. Zeh disclosed serving as a scientific advisor for Surgical Safety Technologies; Dr. Polanco disclosed serving as a consultant for Iota Biosciences and Palisade Bio and as a proctor for Intuitive Surgical.

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

The US Food and Drug Administration has expanded the indication for durvalumab (Imfinzi, AstraZeneca) to include mismatch repair deficient (dMMR) newly diagnosed advanced or recurrent endometrial cancer in combination with carboplatin and paclitaxel followed by single-agent use for maintenance.

Originally approved in 2017, the programmed death ligand 1 inhibitor caries previously approved indications for non–small cell lung cancer, biliary tract cancer, and hepatocellular carcinoma.

Approval of the new indication was based on the phase 3 DUO-E trial, which included 95 women with newly diagnosed advanced or recurrent dMMR endometrial cancer. Patients were randomized to durvalumab 1120 mg or placebo with carboplatin plus paclitaxel every 3 weeks for a maximum of six cycles followed by durvalumab 1500 mg every 4 weeks until disease progression.

Median progression-free survival (PFS) was 7 months in the placebo arm but not reached in the durvalumab group. Overall survival outcomes were immature at the PFS analysis.

A quarter or more of durvalumab patients experienced peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.

The recommended treatment regimen for dMMR endometrial cancer in women who weigh ≥ 30 kg is 1120 mg with carboplatin plus paclitaxel every 3 weeks for six cycles, followed by single-agent durvalumab 1500 mg every 4 weeks.

The price of 2.4 mL of durvalumab at a concentration of 50 mg/mL is $1027, according to drugs.com.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has expanded the indication for durvalumab (Imfinzi, AstraZeneca) to include mismatch repair deficient (dMMR) newly diagnosed advanced or recurrent endometrial cancer in combination with carboplatin and paclitaxel followed by single-agent use for maintenance.

Originally approved in 2017, the programmed death ligand 1 inhibitor caries previously approved indications for non–small cell lung cancer, biliary tract cancer, and hepatocellular carcinoma.

Approval of the new indication was based on the phase 3 DUO-E trial, which included 95 women with newly diagnosed advanced or recurrent dMMR endometrial cancer. Patients were randomized to durvalumab 1120 mg or placebo with carboplatin plus paclitaxel every 3 weeks for a maximum of six cycles followed by durvalumab 1500 mg every 4 weeks until disease progression.

Median progression-free survival (PFS) was 7 months in the placebo arm but not reached in the durvalumab group. Overall survival outcomes were immature at the PFS analysis.

A quarter or more of durvalumab patients experienced peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.

The recommended treatment regimen for dMMR endometrial cancer in women who weigh ≥ 30 kg is 1120 mg with carboplatin plus paclitaxel every 3 weeks for six cycles, followed by single-agent durvalumab 1500 mg every 4 weeks.

The price of 2.4 mL of durvalumab at a concentration of 50 mg/mL is $1027, according to drugs.com.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has expanded the indication for durvalumab (Imfinzi, AstraZeneca) to include mismatch repair deficient (dMMR) newly diagnosed advanced or recurrent endometrial cancer in combination with carboplatin and paclitaxel followed by single-agent use for maintenance.

Originally approved in 2017, the programmed death ligand 1 inhibitor caries previously approved indications for non–small cell lung cancer, biliary tract cancer, and hepatocellular carcinoma.

Approval of the new indication was based on the phase 3 DUO-E trial, which included 95 women with newly diagnosed advanced or recurrent dMMR endometrial cancer. Patients were randomized to durvalumab 1120 mg or placebo with carboplatin plus paclitaxel every 3 weeks for a maximum of six cycles followed by durvalumab 1500 mg every 4 weeks until disease progression.

Median progression-free survival (PFS) was 7 months in the placebo arm but not reached in the durvalumab group. Overall survival outcomes were immature at the PFS analysis.

A quarter or more of durvalumab patients experienced peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.

The recommended treatment regimen for dMMR endometrial cancer in women who weigh ≥ 30 kg is 1120 mg with carboplatin plus paclitaxel every 3 weeks for six cycles, followed by single-agent durvalumab 1500 mg every 4 weeks.

The price of 2.4 mL of durvalumab at a concentration of 50 mg/mL is $1027, according to drugs.com.

A version of this article appeared on Medscape.com.

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

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

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

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

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

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

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

A renowned leader in colorectal cancer research, Scott Kopetz, MD, PhD, was recently honored for helping establish new standards of care for BRAF-mutated metastatic colorectal cancer.

Dr. Kopetz received the AACR-Waun Ki Hong Award in April. The American Association for Cancer Research (AACR) granted Dr. Kopetz this award to recognize his leadership in the development of novel therapies for patients with BRAF-mutated metastatic colon cancer with poor prognoses, according to a statement from the AACR.

logipropreshirocucruphohiwrikudravuspebruuiwrebeserobubrisoshaslimitharibrecihugecugekowreg

What led to your medical career? Growing up, did you always want to be a doctor?

Dr. Kopetz: My interest initially was in engineering. I grew up in Tennessee from a family of engineers and doctors. In college, I completed a degree in biomedical engineering and electrical engineering.

I had the opportunity to spend one summer at the National Institutes of Health, where I did some research on the structure of the HIV integrase enzyme. It was fundamental basic research with some engineering overlay and required spending 4 days a week working in the dark in a laser lab to analyze the structure of this protein.

One day a week, I was at Georgetown in the HIV/AIDS Clinic, where I collected blood samples and saw HIV/AIDS patients. At the end of the summer, I reflected and realized that I really enjoyed that 1 day out of the week, much more than the other 4. I enjoyed working with patients and interacting with people and thought I’d enjoy the more direct way to help patients, so made a pivot into medicine.
 

Was the rest of your medical training more traditional?

Dr. Kopetz: My path was a little atypical for a physician scientist. I pursued a medical degree at Johns Hopkins, did internal medicine training at Duke, and then came down to MD Anderson Cancer Center [in Houston, Texas] to do a fellowship in medical oncology, and also obtained a PhD in cancer biology, where I explored mechanisms of resistance to colorectal cancer treatment.

While a traditional physician scientist typically obtains a PhD training in the middle of their medical school, I completed my medical training and then went back to get a PhD. It was a different, nontraditional route.
 

What is your current role, and what is most inspiring about your work?

Dr. Kopetz: I’ve been at MD Anderson now for 20 years in GI medical oncology. I recently stepped into a new role of helping facilitate translational research at the institution and am now Associate VP for translational research.

I’m excited about where we are in cancer research. I think we’re moving into an era where the amount of information that we can get out of patients and the rapidity in which we can move discoveries is much greater than it has ever been.

Our ability to extract information out of patient biopsies, surgical samples, or even minimally invasive techniques to sample the tumors, such as liquid biopsy, has provided tremendous insights into how tumors are evolving and adapting to therapies and [provides us] opportunities for novel interventions. This opens up ways where I think as a field, we can more readily accelerate our understanding of cancer.

The second component is seeing the rapidity in which we’re now able to execute ideas in the drug development space compared to years before. The pace of new drug development has increased and the innovations in the chemistries have opened up new opportunities and new targets that in the past were considered undruggable. For example, the mutated oncogene, KRAS, was once an extremely challenging therapeutic target and considered undruggable. Mutations in the p53 gene, a tumor suppressor gene, were similarly challenging. I think the convergence of these two trends are going to more rapidly accelerate the advances for our patients. I’m optimistic about the future.
 

Tell us more about the novel therapies for patients with BRAF-mutated metastatic colon cancer for which you were a lead researcher.

Dr. Kopetz: A lot of [my] work goes back over 10 years, where my [research colleagues and I] were targeting the BRAF V600E oncogene in colorectal cancer melanoma and identified that this worked well in melanoma but was relatively inactive in colorectal cancer despite the same drugs and the same mutations. This led to a recognition of optimal combination drugs that really blocked some of the adaptive feedback that we saw in colorectal cancer. This was a key recognition that these tumors, after you block one node of signaling, rapidly adapt and reactivate the signaling through alternate nodes. This finding really resonated with me with my engineering background, thinking about the networks, signaling networks, and the concepts of feedback regulation of complex systems.

The strategy of blocking the primary oncogene and then blocking the feedback mechanisms that the tumors were utilizing was adopted in colorectal cancer through this work. It took us 10 years to get to an FDA approval with this strategy, but it’s really encouraging that we’re now using this strategy and applying it to the new wave of KRAS inhibitors, where the exact same feedback pathway appears to be at play.
 

Does your engineering background impact your work today?

Dr. Kopetz: Yes, I’ve found that my engineering training has provided me with complementary skills that can significantly contribute to the development of innovative technologies, computational approaches, and interdisciplinary strategies for advancing cancer research.

Today, I do a lot of work understanding and recognizing complex networks of signaling, and it’s the same network theories that we learned and developed in engineering.

These same theories are now being applied to biology. For example, we are very interested in how tumors adapt over the longer term, over multiple lines of therapy, where there is both clonal selection and clonal evolution occurring with our various standard-of-care therapies. Our hope is that application of engineering principles can help uncover new vulnerabilities in cancer that weren’t evident when we were thinking about CRC as a static tumor.
 

I understand your recently awarded AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research has special significance to you. Can you explain why that is?

Dr. Kopetz: This holds a special meaning for me, because Dr. Hong provided a lot of guidance [to me] over the years. He was the division head for cancer medicine at MD Anderson for many years and was instrumental in helping advocate [for me] and advance my career as well as the careers of so many others in and outside of the institution. I considered him a key mentor and sponsor. He helped provide me with guidance early in my oncology career, helping me identify high-value projects and critically evaluate research directions to pursue. He also helped me think about how to balance my research portfolio and provided guidance about how to work well within a team.

It’s really humbling to have a reward bearing his name as somebody who I so deeply respected, and I’m so grateful for the impact he had on my life.

A renowned leader in colorectal cancer research, Scott Kopetz, MD, PhD, was recently honored for helping establish new standards of care for BRAF-mutated metastatic colorectal cancer.

Dr. Kopetz received the AACR-Waun Ki Hong Award in April. The American Association for Cancer Research (AACR) granted Dr. Kopetz this award to recognize his leadership in the development of novel therapies for patients with BRAF-mutated metastatic colon cancer with poor prognoses, according to a statement from the AACR.

logipropreshirocucruphohiwrikudravuspebruuiwrebeserobubrisoshaslimitharibrecihugecugekowreg

What led to your medical career? Growing up, did you always want to be a doctor?

Dr. Kopetz: My interest initially was in engineering. I grew up in Tennessee from a family of engineers and doctors. In college, I completed a degree in biomedical engineering and electrical engineering.

I had the opportunity to spend one summer at the National Institutes of Health, where I did some research on the structure of the HIV integrase enzyme. It was fundamental basic research with some engineering overlay and required spending 4 days a week working in the dark in a laser lab to analyze the structure of this protein.

One day a week, I was at Georgetown in the HIV/AIDS Clinic, where I collected blood samples and saw HIV/AIDS patients. At the end of the summer, I reflected and realized that I really enjoyed that 1 day out of the week, much more than the other 4. I enjoyed working with patients and interacting with people and thought I’d enjoy the more direct way to help patients, so made a pivot into medicine.
 

Was the rest of your medical training more traditional?

Dr. Kopetz: My path was a little atypical for a physician scientist. I pursued a medical degree at Johns Hopkins, did internal medicine training at Duke, and then came down to MD Anderson Cancer Center [in Houston, Texas] to do a fellowship in medical oncology, and also obtained a PhD in cancer biology, where I explored mechanisms of resistance to colorectal cancer treatment.

While a traditional physician scientist typically obtains a PhD training in the middle of their medical school, I completed my medical training and then went back to get a PhD. It was a different, nontraditional route.
 

What is your current role, and what is most inspiring about your work?

Dr. Kopetz: I’ve been at MD Anderson now for 20 years in GI medical oncology. I recently stepped into a new role of helping facilitate translational research at the institution and am now Associate VP for translational research.

I’m excited about where we are in cancer research. I think we’re moving into an era where the amount of information that we can get out of patients and the rapidity in which we can move discoveries is much greater than it has ever been.

Our ability to extract information out of patient biopsies, surgical samples, or even minimally invasive techniques to sample the tumors, such as liquid biopsy, has provided tremendous insights into how tumors are evolving and adapting to therapies and [provides us] opportunities for novel interventions. This opens up ways where I think as a field, we can more readily accelerate our understanding of cancer.

The second component is seeing the rapidity in which we’re now able to execute ideas in the drug development space compared to years before. The pace of new drug development has increased and the innovations in the chemistries have opened up new opportunities and new targets that in the past were considered undruggable. For example, the mutated oncogene, KRAS, was once an extremely challenging therapeutic target and considered undruggable. Mutations in the p53 gene, a tumor suppressor gene, were similarly challenging. I think the convergence of these two trends are going to more rapidly accelerate the advances for our patients. I’m optimistic about the future.
 

Tell us more about the novel therapies for patients with BRAF-mutated metastatic colon cancer for which you were a lead researcher.

Dr. Kopetz: A lot of [my] work goes back over 10 years, where my [research colleagues and I] were targeting the BRAF V600E oncogene in colorectal cancer melanoma and identified that this worked well in melanoma but was relatively inactive in colorectal cancer despite the same drugs and the same mutations. This led to a recognition of optimal combination drugs that really blocked some of the adaptive feedback that we saw in colorectal cancer. This was a key recognition that these tumors, after you block one node of signaling, rapidly adapt and reactivate the signaling through alternate nodes. This finding really resonated with me with my engineering background, thinking about the networks, signaling networks, and the concepts of feedback regulation of complex systems.

The strategy of blocking the primary oncogene and then blocking the feedback mechanisms that the tumors were utilizing was adopted in colorectal cancer through this work. It took us 10 years to get to an FDA approval with this strategy, but it’s really encouraging that we’re now using this strategy and applying it to the new wave of KRAS inhibitors, where the exact same feedback pathway appears to be at play.
 

Does your engineering background impact your work today?

Dr. Kopetz: Yes, I’ve found that my engineering training has provided me with complementary skills that can significantly contribute to the development of innovative technologies, computational approaches, and interdisciplinary strategies for advancing cancer research.

Today, I do a lot of work understanding and recognizing complex networks of signaling, and it’s the same network theories that we learned and developed in engineering.

These same theories are now being applied to biology. For example, we are very interested in how tumors adapt over the longer term, over multiple lines of therapy, where there is both clonal selection and clonal evolution occurring with our various standard-of-care therapies. Our hope is that application of engineering principles can help uncover new vulnerabilities in cancer that weren’t evident when we were thinking about CRC as a static tumor.
 

I understand your recently awarded AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research has special significance to you. Can you explain why that is?

Dr. Kopetz: This holds a special meaning for me, because Dr. Hong provided a lot of guidance [to me] over the years. He was the division head for cancer medicine at MD Anderson for many years and was instrumental in helping advocate [for me] and advance my career as well as the careers of so many others in and outside of the institution. I considered him a key mentor and sponsor. He helped provide me with guidance early in my oncology career, helping me identify high-value projects and critically evaluate research directions to pursue. He also helped me think about how to balance my research portfolio and provided guidance about how to work well within a team.

It’s really humbling to have a reward bearing his name as somebody who I so deeply respected, and I’m so grateful for the impact he had on my life.

A renowned leader in colorectal cancer research, Scott Kopetz, MD, PhD, was recently honored for helping establish new standards of care for BRAF-mutated metastatic colorectal cancer.

Dr. Kopetz received the AACR-Waun Ki Hong Award in April. The American Association for Cancer Research (AACR) granted Dr. Kopetz this award to recognize his leadership in the development of novel therapies for patients with BRAF-mutated metastatic colon cancer with poor prognoses, according to a statement from the AACR.

logipropreshirocucruphohiwrikudravuspebruuiwrebeserobubrisoshaslimitharibrecihugecugekowreg

What led to your medical career? Growing up, did you always want to be a doctor?

Dr. Kopetz: My interest initially was in engineering. I grew up in Tennessee from a family of engineers and doctors. In college, I completed a degree in biomedical engineering and electrical engineering.

I had the opportunity to spend one summer at the National Institutes of Health, where I did some research on the structure of the HIV integrase enzyme. It was fundamental basic research with some engineering overlay and required spending 4 days a week working in the dark in a laser lab to analyze the structure of this protein.

One day a week, I was at Georgetown in the HIV/AIDS Clinic, where I collected blood samples and saw HIV/AIDS patients. At the end of the summer, I reflected and realized that I really enjoyed that 1 day out of the week, much more than the other 4. I enjoyed working with patients and interacting with people and thought I’d enjoy the more direct way to help patients, so made a pivot into medicine.
 

Was the rest of your medical training more traditional?

Dr. Kopetz: My path was a little atypical for a physician scientist. I pursued a medical degree at Johns Hopkins, did internal medicine training at Duke, and then came down to MD Anderson Cancer Center [in Houston, Texas] to do a fellowship in medical oncology, and also obtained a PhD in cancer biology, where I explored mechanisms of resistance to colorectal cancer treatment.

While a traditional physician scientist typically obtains a PhD training in the middle of their medical school, I completed my medical training and then went back to get a PhD. It was a different, nontraditional route.
 

What is your current role, and what is most inspiring about your work?

Dr. Kopetz: I’ve been at MD Anderson now for 20 years in GI medical oncology. I recently stepped into a new role of helping facilitate translational research at the institution and am now Associate VP for translational research.

I’m excited about where we are in cancer research. I think we’re moving into an era where the amount of information that we can get out of patients and the rapidity in which we can move discoveries is much greater than it has ever been.

Our ability to extract information out of patient biopsies, surgical samples, or even minimally invasive techniques to sample the tumors, such as liquid biopsy, has provided tremendous insights into how tumors are evolving and adapting to therapies and [provides us] opportunities for novel interventions. This opens up ways where I think as a field, we can more readily accelerate our understanding of cancer.

The second component is seeing the rapidity in which we’re now able to execute ideas in the drug development space compared to years before. The pace of new drug development has increased and the innovations in the chemistries have opened up new opportunities and new targets that in the past were considered undruggable. For example, the mutated oncogene, KRAS, was once an extremely challenging therapeutic target and considered undruggable. Mutations in the p53 gene, a tumor suppressor gene, were similarly challenging. I think the convergence of these two trends are going to more rapidly accelerate the advances for our patients. I’m optimistic about the future.
 

Tell us more about the novel therapies for patients with BRAF-mutated metastatic colon cancer for which you were a lead researcher.

Dr. Kopetz: A lot of [my] work goes back over 10 years, where my [research colleagues and I] were targeting the BRAF V600E oncogene in colorectal cancer melanoma and identified that this worked well in melanoma but was relatively inactive in colorectal cancer despite the same drugs and the same mutations. This led to a recognition of optimal combination drugs that really blocked some of the adaptive feedback that we saw in colorectal cancer. This was a key recognition that these tumors, after you block one node of signaling, rapidly adapt and reactivate the signaling through alternate nodes. This finding really resonated with me with my engineering background, thinking about the networks, signaling networks, and the concepts of feedback regulation of complex systems.

The strategy of blocking the primary oncogene and then blocking the feedback mechanisms that the tumors were utilizing was adopted in colorectal cancer through this work. It took us 10 years to get to an FDA approval with this strategy, but it’s really encouraging that we’re now using this strategy and applying it to the new wave of KRAS inhibitors, where the exact same feedback pathway appears to be at play.
 

Does your engineering background impact your work today?

Dr. Kopetz: Yes, I’ve found that my engineering training has provided me with complementary skills that can significantly contribute to the development of innovative technologies, computational approaches, and interdisciplinary strategies for advancing cancer research.

Today, I do a lot of work understanding and recognizing complex networks of signaling, and it’s the same network theories that we learned and developed in engineering.

These same theories are now being applied to biology. For example, we are very interested in how tumors adapt over the longer term, over multiple lines of therapy, where there is both clonal selection and clonal evolution occurring with our various standard-of-care therapies. Our hope is that application of engineering principles can help uncover new vulnerabilities in cancer that weren’t evident when we were thinking about CRC as a static tumor.
 

I understand your recently awarded AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research has special significance to you. Can you explain why that is?

Dr. Kopetz: This holds a special meaning for me, because Dr. Hong provided a lot of guidance [to me] over the years. He was the division head for cancer medicine at MD Anderson for many years and was instrumental in helping advocate [for me] and advance my career as well as the careers of so many others in and outside of the institution. I considered him a key mentor and sponsor. He helped provide me with guidance early in my oncology career, helping me identify high-value projects and critically evaluate research directions to pursue. He also helped me think about how to balance my research portfolio and provided guidance about how to work well within a team.

It’s really humbling to have a reward bearing his name as somebody who I so deeply respected, and I’m so grateful for the impact he had on my life.