Patient & Survivor Care

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

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

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

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

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

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

TOPLINE:

Patients with metastatic hormone-sensitive prostate cancer and baseline bone pain at diagnosis have worse overall survival compared to those without bone pain, a post hoc study found.

METHODOLOGY:

• Prostate cancer often metastasizes to the bones, leading to pain and a reduced quality of life. While the relationship between bone pain and overall survival in metastatic, castration-resistant prostate cancer is well-documented, its impact in metastatic hormone-sensitive prostate cancer is less clear.
• Researchers conducted a post hoc secondary analysis using data from the SWOG-1216 phase 3 randomized clinical trial, which included 1279 men diagnosed with metastatic hormone-sensitive prostate cancer from 248 centers across the United States. Patients had received androgen deprivation therapy either with orteronel or bicalutamide.
• Among the 1197 patients (median age, 67.6 years) with data on bone pain included in the secondary analysis, 301 (23.5%) reported bone pain at baseline.
• The primary outcome was overall survival; secondary outcomes included progression-free survival and prostate-specific antigen response.

TAKEAWAY:

• The median overall survival for patients with baseline bone pain was 3.9 years compared with not reached (95% CI, 6.6 years to not reached) for those without bone pain at a median follow-up of 4 years (adjusted hazard ratio [aHR], 1.66; P < .001).
• Similarly, patients with bone pain had a shorter progression-free survival vs those without bone pain (median, 1.3 years vs 3.7 years; aHR, 1.46; P < .001).
• The complete prostate-specific antigen response rate at 7 months was also lower for patients with baseline bone pain (46.3% vs 66.3%; P < .001).

IN PRACTICE:

Patients with metastatic hormone-sensitive prostate cancer “with baseline bone pain had worse survival outcomes than those without baseline bone pain,” the authors wrote. “These results highlight the need to consider bone pain in prognostic modeling, treatment selection, patient monitoring, and follow-up and suggest prioritizing these patients for clinical trials and immediate systemic treatment initiation.”

SOURCE:

The study, led by Georges Gebrael, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, was published online in JAMA Network Open.

LIMITATIONS:

The post hoc design may introduce bias. Orteronel failed to receive regulatory approval, which may affect the generalizability of the findings. In addition, the study did not account for synchronous vs metachronous disease status, a known established prognostic factor.

DISCLOSURES:

The study was funded by the National Institutes of Health/National Cancer Institute and Millennium Pharmaceuticals (Takeda Oncology Company). Several authors declared ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with metastatic hormone-sensitive prostate cancer and baseline bone pain at diagnosis have worse overall survival compared to those without bone pain, a post hoc study found.

METHODOLOGY:

• Prostate cancer often metastasizes to the bones, leading to pain and a reduced quality of life. While the relationship between bone pain and overall survival in metastatic, castration-resistant prostate cancer is well-documented, its impact in metastatic hormone-sensitive prostate cancer is less clear.
• Researchers conducted a post hoc secondary analysis using data from the SWOG-1216 phase 3 randomized clinical trial, which included 1279 men diagnosed with metastatic hormone-sensitive prostate cancer from 248 centers across the United States. Patients had received androgen deprivation therapy either with orteronel or bicalutamide.
• Among the 1197 patients (median age, 67.6 years) with data on bone pain included in the secondary analysis, 301 (23.5%) reported bone pain at baseline.
• The primary outcome was overall survival; secondary outcomes included progression-free survival and prostate-specific antigen response.

TAKEAWAY:

• The median overall survival for patients with baseline bone pain was 3.9 years compared with not reached (95% CI, 6.6 years to not reached) for those without bone pain at a median follow-up of 4 years (adjusted hazard ratio [aHR], 1.66; P < .001).
• Similarly, patients with bone pain had a shorter progression-free survival vs those without bone pain (median, 1.3 years vs 3.7 years; aHR, 1.46; P < .001).
• The complete prostate-specific antigen response rate at 7 months was also lower for patients with baseline bone pain (46.3% vs 66.3%; P < .001).

IN PRACTICE:

Patients with metastatic hormone-sensitive prostate cancer “with baseline bone pain had worse survival outcomes than those without baseline bone pain,” the authors wrote. “These results highlight the need to consider bone pain in prognostic modeling, treatment selection, patient monitoring, and follow-up and suggest prioritizing these patients for clinical trials and immediate systemic treatment initiation.”

SOURCE:

The study, led by Georges Gebrael, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, was published online in JAMA Network Open.

LIMITATIONS:

The post hoc design may introduce bias. Orteronel failed to receive regulatory approval, which may affect the generalizability of the findings. In addition, the study did not account for synchronous vs metachronous disease status, a known established prognostic factor.

DISCLOSURES:

The study was funded by the National Institutes of Health/National Cancer Institute and Millennium Pharmaceuticals (Takeda Oncology Company). Several authors declared ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with metastatic hormone-sensitive prostate cancer and baseline bone pain at diagnosis have worse overall survival compared to those without bone pain, a post hoc study found.

METHODOLOGY:

• Prostate cancer often metastasizes to the bones, leading to pain and a reduced quality of life. While the relationship between bone pain and overall survival in metastatic, castration-resistant prostate cancer is well-documented, its impact in metastatic hormone-sensitive prostate cancer is less clear.
• Researchers conducted a post hoc secondary analysis using data from the SWOG-1216 phase 3 randomized clinical trial, which included 1279 men diagnosed with metastatic hormone-sensitive prostate cancer from 248 centers across the United States. Patients had received androgen deprivation therapy either with orteronel or bicalutamide.
• Among the 1197 patients (median age, 67.6 years) with data on bone pain included in the secondary analysis, 301 (23.5%) reported bone pain at baseline.
• The primary outcome was overall survival; secondary outcomes included progression-free survival and prostate-specific antigen response.

TAKEAWAY:

• The median overall survival for patients with baseline bone pain was 3.9 years compared with not reached (95% CI, 6.6 years to not reached) for those without bone pain at a median follow-up of 4 years (adjusted hazard ratio [aHR], 1.66; P < .001).
• Similarly, patients with bone pain had a shorter progression-free survival vs those without bone pain (median, 1.3 years vs 3.7 years; aHR, 1.46; P < .001).
• The complete prostate-specific antigen response rate at 7 months was also lower for patients with baseline bone pain (46.3% vs 66.3%; P < .001).

IN PRACTICE:

Patients with metastatic hormone-sensitive prostate cancer “with baseline bone pain had worse survival outcomes than those without baseline bone pain,” the authors wrote. “These results highlight the need to consider bone pain in prognostic modeling, treatment selection, patient monitoring, and follow-up and suggest prioritizing these patients for clinical trials and immediate systemic treatment initiation.”

SOURCE:

The study, led by Georges Gebrael, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, was published online in JAMA Network Open.

LIMITATIONS:

The post hoc design may introduce bias. Orteronel failed to receive regulatory approval, which may affect the generalizability of the findings. In addition, the study did not account for synchronous vs metachronous disease status, a known established prognostic factor.

DISCLOSURES:

The study was funded by the National Institutes of Health/National Cancer Institute and Millennium Pharmaceuticals (Takeda Oncology Company). Several authors declared ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

In the last 10 years, clinical outcomes have improved for patients with unresectable hepatocellular carcinoma (uHCC). The cancer generally comes with chronic liver inflammation, and liver cirrhosis is present in up to 80% of cases. The level of liver dysfunction helps determine the prognosis, but it also may affect the safety of delivering anticancer treatment.

Clinical trials that have tested systemic immunotherapies have excluded patients who don’t fall into the Child-Pugh class A criteria (CP-A) for liver disease, which is the least severe of the Child-Pugh classes A-C. Therefore, there has been much debate about whether patients who have more liver disease (moderate liver dysfunction) and fit under CP-B criteria, instead of CP-A, should be treated with immune checkpoint inhibitor (ICI) therapy or best supportive care (BSC).

A new study, led by Claudia Angela Maria Fulgenzi, MD, with the Department of Surgery and Cancer at the Imperial College London, England, published in JAMA Oncology on July 18, uses an alternative way to compare outcomes following two different paths of care for uHCC patients with moderate liver dysfunction.
 

How was the study done and what did the investigators find?

Researchers performed a retrospective, multicenter, international clinical case series of patients treated in routine practice in tertiary care centers across Europe, the United States, and Asia. They compared data from uHCC patients with CP-B who were receiving first-line ICI-based treatment regimens (n = 187) with a cohort of matched patients with CP-B receiving BSC (n = 156). The first-line immunotherapies were the monotherapy nivolumab or the combination (atezolizumab plus bevacizumab).

Immunotherapy was linked with significantly lower risk of death, compared with best supportive care.

ICI exposure was associated with a reduction of about 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001).
 

Is immunotherapy or best supportive care the superior treatment?

The authors wrote that the results point to “improved survival in association with ICI treatment, compared with BSC in patients with uHCC with CP-B liver dysfunction.”

According to the study’s senior author David Pinato, MD, PhD, “this is the first study to suggest that there might be an advantage [of treatment with immunotherapy] in a proportion of people with Child-Pugh B liver dysfunction and particularly so in those patients with more limited disease and portal vein tumor thrombosis.”
 

Will the findings of this study make treatment allocation for patients with uHCC and moderate liver dysfunction (CP-B) less controversial?

Because it is a retrospective study, Dr. Pinato said in an interview, that the findings are not definitive, but can be used to inform future randomized controlled trials.

Dr. Pinato, who is also with the Imperial College London, added that the findings may also introduce a new question.

Although the study was not powered to look at survival differences across the two immunotherapy options given to the patients, there did not seem to be a striking difference between using one immunotherapy (nivolumab) or a combination (atezolizumab plus bevacizumab), he said.

“This is quite important because we know that combinations are significantly superior to monotherapy in patients with normal liver function but based on our study we might say that this provides preliminary evidence that [superiority of combination therapy] might not be true if the liver function is worse.”
 

What do these findings add to the literature about how best to treat patients with uHCC and suboptimal liver function?

Without evidence of efficacy and safety for the group in previous studies, the widespread recommendation for those with moderate dysfunction has been BSC.

These findings “pave the way to select potential patient subgroups in clinical practice,” Dr. Pinato said. It also suggests that the safety level of immunotherapy treatments is acceptable in this patient population, so they are not necessarily disadvantaged compared to patients with more preserved liver function.

“This is the best level of evidence currently available to guide treatment decisions in patients with Child-Pugh B who have been universally excluded by prospective clinical trials and for whom there is no randomized comparison,” Dr. Pinato said.

Dr. Pinato reported personal fees from Roche, AstraZeneca, Eisai, Mina Therapeutics, Starpharma, Lift Biosciences, Boston Scientific, and Avammune, and grants from GSK, MSD, and BMS outside the submitted work. Dr. Fulgenzi has no disclosures. Other authors of the new research have multiple ties with pharmaceutical companies. Complete disclosures are available with the full text of the journal article.

In the last 10 years, clinical outcomes have improved for patients with unresectable hepatocellular carcinoma (uHCC). The cancer generally comes with chronic liver inflammation, and liver cirrhosis is present in up to 80% of cases. The level of liver dysfunction helps determine the prognosis, but it also may affect the safety of delivering anticancer treatment.

Clinical trials that have tested systemic immunotherapies have excluded patients who don’t fall into the Child-Pugh class A criteria (CP-A) for liver disease, which is the least severe of the Child-Pugh classes A-C. Therefore, there has been much debate about whether patients who have more liver disease (moderate liver dysfunction) and fit under CP-B criteria, instead of CP-A, should be treated with immune checkpoint inhibitor (ICI) therapy or best supportive care (BSC).

A new study, led by Claudia Angela Maria Fulgenzi, MD, with the Department of Surgery and Cancer at the Imperial College London, England, published in JAMA Oncology on July 18, uses an alternative way to compare outcomes following two different paths of care for uHCC patients with moderate liver dysfunction.
 

How was the study done and what did the investigators find?

Researchers performed a retrospective, multicenter, international clinical case series of patients treated in routine practice in tertiary care centers across Europe, the United States, and Asia. They compared data from uHCC patients with CP-B who were receiving first-line ICI-based treatment regimens (n = 187) with a cohort of matched patients with CP-B receiving BSC (n = 156). The first-line immunotherapies were the monotherapy nivolumab or the combination (atezolizumab plus bevacizumab).

Immunotherapy was linked with significantly lower risk of death, compared with best supportive care.

ICI exposure was associated with a reduction of about 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001).
 

Is immunotherapy or best supportive care the superior treatment?

The authors wrote that the results point to “improved survival in association with ICI treatment, compared with BSC in patients with uHCC with CP-B liver dysfunction.”

According to the study’s senior author David Pinato, MD, PhD, “this is the first study to suggest that there might be an advantage [of treatment with immunotherapy] in a proportion of people with Child-Pugh B liver dysfunction and particularly so in those patients with more limited disease and portal vein tumor thrombosis.”
 

Will the findings of this study make treatment allocation for patients with uHCC and moderate liver dysfunction (CP-B) less controversial?

Because it is a retrospective study, Dr. Pinato said in an interview, that the findings are not definitive, but can be used to inform future randomized controlled trials.

Dr. Pinato, who is also with the Imperial College London, added that the findings may also introduce a new question.

Although the study was not powered to look at survival differences across the two immunotherapy options given to the patients, there did not seem to be a striking difference between using one immunotherapy (nivolumab) or a combination (atezolizumab plus bevacizumab), he said.

“This is quite important because we know that combinations are significantly superior to monotherapy in patients with normal liver function but based on our study we might say that this provides preliminary evidence that [superiority of combination therapy] might not be true if the liver function is worse.”
 

What do these findings add to the literature about how best to treat patients with uHCC and suboptimal liver function?

Without evidence of efficacy and safety for the group in previous studies, the widespread recommendation for those with moderate dysfunction has been BSC.

These findings “pave the way to select potential patient subgroups in clinical practice,” Dr. Pinato said. It also suggests that the safety level of immunotherapy treatments is acceptable in this patient population, so they are not necessarily disadvantaged compared to patients with more preserved liver function.

“This is the best level of evidence currently available to guide treatment decisions in patients with Child-Pugh B who have been universally excluded by prospective clinical trials and for whom there is no randomized comparison,” Dr. Pinato said.

Dr. Pinato reported personal fees from Roche, AstraZeneca, Eisai, Mina Therapeutics, Starpharma, Lift Biosciences, Boston Scientific, and Avammune, and grants from GSK, MSD, and BMS outside the submitted work. Dr. Fulgenzi has no disclosures. Other authors of the new research have multiple ties with pharmaceutical companies. Complete disclosures are available with the full text of the journal article.

In the last 10 years, clinical outcomes have improved for patients with unresectable hepatocellular carcinoma (uHCC). The cancer generally comes with chronic liver inflammation, and liver cirrhosis is present in up to 80% of cases. The level of liver dysfunction helps determine the prognosis, but it also may affect the safety of delivering anticancer treatment.

Clinical trials that have tested systemic immunotherapies have excluded patients who don’t fall into the Child-Pugh class A criteria (CP-A) for liver disease, which is the least severe of the Child-Pugh classes A-C. Therefore, there has been much debate about whether patients who have more liver disease (moderate liver dysfunction) and fit under CP-B criteria, instead of CP-A, should be treated with immune checkpoint inhibitor (ICI) therapy or best supportive care (BSC).

A new study, led by Claudia Angela Maria Fulgenzi, MD, with the Department of Surgery and Cancer at the Imperial College London, England, published in JAMA Oncology on July 18, uses an alternative way to compare outcomes following two different paths of care for uHCC patients with moderate liver dysfunction.
 

How was the study done and what did the investigators find?

Researchers performed a retrospective, multicenter, international clinical case series of patients treated in routine practice in tertiary care centers across Europe, the United States, and Asia. They compared data from uHCC patients with CP-B who were receiving first-line ICI-based treatment regimens (n = 187) with a cohort of matched patients with CP-B receiving BSC (n = 156). The first-line immunotherapies were the monotherapy nivolumab or the combination (atezolizumab plus bevacizumab).

Immunotherapy was linked with significantly lower risk of death, compared with best supportive care.

ICI exposure was associated with a reduction of about 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001).
 

Is immunotherapy or best supportive care the superior treatment?

The authors wrote that the results point to “improved survival in association with ICI treatment, compared with BSC in patients with uHCC with CP-B liver dysfunction.”

According to the study’s senior author David Pinato, MD, PhD, “this is the first study to suggest that there might be an advantage [of treatment with immunotherapy] in a proportion of people with Child-Pugh B liver dysfunction and particularly so in those patients with more limited disease and portal vein tumor thrombosis.”
 

Will the findings of this study make treatment allocation for patients with uHCC and moderate liver dysfunction (CP-B) less controversial?

Because it is a retrospective study, Dr. Pinato said in an interview, that the findings are not definitive, but can be used to inform future randomized controlled trials.

Dr. Pinato, who is also with the Imperial College London, added that the findings may also introduce a new question.

Although the study was not powered to look at survival differences across the two immunotherapy options given to the patients, there did not seem to be a striking difference between using one immunotherapy (nivolumab) or a combination (atezolizumab plus bevacizumab), he said.

“This is quite important because we know that combinations are significantly superior to monotherapy in patients with normal liver function but based on our study we might say that this provides preliminary evidence that [superiority of combination therapy] might not be true if the liver function is worse.”
 

What do these findings add to the literature about how best to treat patients with uHCC and suboptimal liver function?

Without evidence of efficacy and safety for the group in previous studies, the widespread recommendation for those with moderate dysfunction has been BSC.

These findings “pave the way to select potential patient subgroups in clinical practice,” Dr. Pinato said. It also suggests that the safety level of immunotherapy treatments is acceptable in this patient population, so they are not necessarily disadvantaged compared to patients with more preserved liver function.

“This is the best level of evidence currently available to guide treatment decisions in patients with Child-Pugh B who have been universally excluded by prospective clinical trials and for whom there is no randomized comparison,” Dr. Pinato said.

Dr. Pinato reported personal fees from Roche, AstraZeneca, Eisai, Mina Therapeutics, Starpharma, Lift Biosciences, Boston Scientific, and Avammune, and grants from GSK, MSD, and BMS outside the submitted work. Dr. Fulgenzi has no disclosures. Other authors of the new research have multiple ties with pharmaceutical companies. Complete disclosures are available with the full text of the journal article.

Total mesometrial resection (TMMR) is associated with significantly longer recurrence-free survival (RFS) and overall survival (OS) than standard treatment for patients with early-stage cervical cancer, while outcomes were not different among those with locally advanced disease, according to a new study.

These findings suggest that TMMR may be considered a primary treatment option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment, reported lead author Henrik Falconer, MD, PhD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.
 

What is the rationale behind TMMR?

“Current international guidelines [for cervical cancer] are primarily based on retrospective case series and a small number of outdated randomized controlled trials,” the investigators wrote in EClinicalMedicine, part of The Lancet publication platform. “The stage-dependent treatment recommendations, with surgery advised for early-stage and radiation therapy for locally advanced disease, may be considered too simplistic, suggesting that early stages of cervical cancer cannot be controlled with surgical resection alone or that locally advanced cervical cancer is inoperable.”

This mindset, they noted, overlooks the complexities of cancer spread. In contrast, TMMR and similar surgical approaches based on the cancer field model are mapped along routes of locoregional dissemination, leading to “excellent local control” in more than 600 cases at the University Hospital of Leipzig, Leipzig, Germany.

To date, however, TMMR’s adoption has been limited, and it has not been compared directly with current guideline treatments, prompting the present study.
 

What methods were used to compare TMMR with standard treatment?

The study compared TMMR plus therapeutic lymph node dissection (tLND) without adjuvant radiation versus standard treatment (ST) for early-stage (FIGO 2009 IB1, IIA1) and locally advanced (FIGO 2009 IB2, IIA2, IIB) cervical cancer. Standard treatment for patients with early-stage disease involved radical hysterectomy and pelvic lymphadenectomy, with adjuvant chemoradiation dependent upon final pathology. Those with locally advanced disease received definitive chemoradiation.

Data for the standard treatment group were drawn from population-based registries in Sweden, while those for the TMMR group came from the Leipzig Mesometrial Resection Study Database. The final dataset included 1,007 women treated between 2011 and 2020, with 733 undergoing standard treatment and 274 receiving TMMR.

Outcomes included RFS and OS, adjusted for clinical and tumor-related variables.
 

How did TMMR compare with standard treatment?

TMMR was associated with superior oncologic outcomes compared with standard treatment for early-stage cervical cancer.

Specifically, 5-year RFS was 91.2% for TMMR versus 81.8% for standard therapy (P = .002). In the adjusted analysis, TMMR was associated with a significantly lower hazard of recurrence (hazard ratio [HR], 0.39; 95% CI, 0.22–0.69) and death (HR, 0.42; 95% CI, 0.21-0.86). Also favoring TMMR, absolute difference in the risk of recurrence at 5 years was 9.4% (95% CI 3.2–15.7). In addition, 5-year OS was better in the TMMR group, at 93.3%, compared with 90.3% for standard treatment (P = .034).

Among patients with locally advanced disease, no significant differences in RFS or OS were observed.
 

Are these data strong enough to make TMMR the new standard treatment?

Dr. Falconer and colleagues concluded that TMMR with tLND “may replace the standard treatment approach in early-stage cervical cancer and furthermore be evaluated as an option in locally advanced cervical cancer confined to the Müllerian compartment.”

While the investigators anticipated demands for randomized controlled trials, they questioned the value of such studies, suggesting that any control arm would be “based on inconsistent or flawed concepts.”

How does TMMR fit into the current treatment landscape for cervical cancer?

“This is a very niche surgery that most places don’t do,” Dr. Modesitt said.

She pointed out that “multiple variations” on the standard radical hysterectomy have been proposed in the past, such as the laterally extended endopelvic resection.

“[TMMR] is not a new concept,” she said. “It’s just a question of how radical it is.”

Instead of developing new types of radical surgery, she said, the trend in the United States is toward de-escalation of surgical treatments altogether, with greater reliance upon medical options, such as immunotherapy.

“[This study] is thought provoking, and I applaud them for doing it,” Dr. Modesitt said. “But I’m not going to go out and do that on my next patient.”

This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden). Dr. Falconer is a board member of Surgical Science.

Total mesometrial resection (TMMR) is associated with significantly longer recurrence-free survival (RFS) and overall survival (OS) than standard treatment for patients with early-stage cervical cancer, while outcomes were not different among those with locally advanced disease, according to a new study.

These findings suggest that TMMR may be considered a primary treatment option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment, reported lead author Henrik Falconer, MD, PhD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.
 

What is the rationale behind TMMR?

“Current international guidelines [for cervical cancer] are primarily based on retrospective case series and a small number of outdated randomized controlled trials,” the investigators wrote in EClinicalMedicine, part of The Lancet publication platform. “The stage-dependent treatment recommendations, with surgery advised for early-stage and radiation therapy for locally advanced disease, may be considered too simplistic, suggesting that early stages of cervical cancer cannot be controlled with surgical resection alone or that locally advanced cervical cancer is inoperable.”

This mindset, they noted, overlooks the complexities of cancer spread. In contrast, TMMR and similar surgical approaches based on the cancer field model are mapped along routes of locoregional dissemination, leading to “excellent local control” in more than 600 cases at the University Hospital of Leipzig, Leipzig, Germany.

To date, however, TMMR’s adoption has been limited, and it has not been compared directly with current guideline treatments, prompting the present study.
 

What methods were used to compare TMMR with standard treatment?

The study compared TMMR plus therapeutic lymph node dissection (tLND) without adjuvant radiation versus standard treatment (ST) for early-stage (FIGO 2009 IB1, IIA1) and locally advanced (FIGO 2009 IB2, IIA2, IIB) cervical cancer. Standard treatment for patients with early-stage disease involved radical hysterectomy and pelvic lymphadenectomy, with adjuvant chemoradiation dependent upon final pathology. Those with locally advanced disease received definitive chemoradiation.

Data for the standard treatment group were drawn from population-based registries in Sweden, while those for the TMMR group came from the Leipzig Mesometrial Resection Study Database. The final dataset included 1,007 women treated between 2011 and 2020, with 733 undergoing standard treatment and 274 receiving TMMR.

Outcomes included RFS and OS, adjusted for clinical and tumor-related variables.
 

How did TMMR compare with standard treatment?

TMMR was associated with superior oncologic outcomes compared with standard treatment for early-stage cervical cancer.

Specifically, 5-year RFS was 91.2% for TMMR versus 81.8% for standard therapy (P = .002). In the adjusted analysis, TMMR was associated with a significantly lower hazard of recurrence (hazard ratio [HR], 0.39; 95% CI, 0.22–0.69) and death (HR, 0.42; 95% CI, 0.21-0.86). Also favoring TMMR, absolute difference in the risk of recurrence at 5 years was 9.4% (95% CI 3.2–15.7). In addition, 5-year OS was better in the TMMR group, at 93.3%, compared with 90.3% for standard treatment (P = .034).

Among patients with locally advanced disease, no significant differences in RFS or OS were observed.
 

Are these data strong enough to make TMMR the new standard treatment?

Dr. Falconer and colleagues concluded that TMMR with tLND “may replace the standard treatment approach in early-stage cervical cancer and furthermore be evaluated as an option in locally advanced cervical cancer confined to the Müllerian compartment.”

While the investigators anticipated demands for randomized controlled trials, they questioned the value of such studies, suggesting that any control arm would be “based on inconsistent or flawed concepts.”

How does TMMR fit into the current treatment landscape for cervical cancer?

“This is a very niche surgery that most places don’t do,” Dr. Modesitt said.

She pointed out that “multiple variations” on the standard radical hysterectomy have been proposed in the past, such as the laterally extended endopelvic resection.

“[TMMR] is not a new concept,” she said. “It’s just a question of how radical it is.”

Instead of developing new types of radical surgery, she said, the trend in the United States is toward de-escalation of surgical treatments altogether, with greater reliance upon medical options, such as immunotherapy.

“[This study] is thought provoking, and I applaud them for doing it,” Dr. Modesitt said. “But I’m not going to go out and do that on my next patient.”

This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden). Dr. Falconer is a board member of Surgical Science.

Total mesometrial resection (TMMR) is associated with significantly longer recurrence-free survival (RFS) and overall survival (OS) than standard treatment for patients with early-stage cervical cancer, while outcomes were not different among those with locally advanced disease, according to a new study.

These findings suggest that TMMR may be considered a primary treatment option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment, reported lead author Henrik Falconer, MD, PhD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.
 

What is the rationale behind TMMR?

“Current international guidelines [for cervical cancer] are primarily based on retrospective case series and a small number of outdated randomized controlled trials,” the investigators wrote in EClinicalMedicine, part of The Lancet publication platform. “The stage-dependent treatment recommendations, with surgery advised for early-stage and radiation therapy for locally advanced disease, may be considered too simplistic, suggesting that early stages of cervical cancer cannot be controlled with surgical resection alone or that locally advanced cervical cancer is inoperable.”

This mindset, they noted, overlooks the complexities of cancer spread. In contrast, TMMR and similar surgical approaches based on the cancer field model are mapped along routes of locoregional dissemination, leading to “excellent local control” in more than 600 cases at the University Hospital of Leipzig, Leipzig, Germany.

To date, however, TMMR’s adoption has been limited, and it has not been compared directly with current guideline treatments, prompting the present study.
 

What methods were used to compare TMMR with standard treatment?

The study compared TMMR plus therapeutic lymph node dissection (tLND) without adjuvant radiation versus standard treatment (ST) for early-stage (FIGO 2009 IB1, IIA1) and locally advanced (FIGO 2009 IB2, IIA2, IIB) cervical cancer. Standard treatment for patients with early-stage disease involved radical hysterectomy and pelvic lymphadenectomy, with adjuvant chemoradiation dependent upon final pathology. Those with locally advanced disease received definitive chemoradiation.

Data for the standard treatment group were drawn from population-based registries in Sweden, while those for the TMMR group came from the Leipzig Mesometrial Resection Study Database. The final dataset included 1,007 women treated between 2011 and 2020, with 733 undergoing standard treatment and 274 receiving TMMR.

Outcomes included RFS and OS, adjusted for clinical and tumor-related variables.
 

How did TMMR compare with standard treatment?

TMMR was associated with superior oncologic outcomes compared with standard treatment for early-stage cervical cancer.

Specifically, 5-year RFS was 91.2% for TMMR versus 81.8% for standard therapy (P = .002). In the adjusted analysis, TMMR was associated with a significantly lower hazard of recurrence (hazard ratio [HR], 0.39; 95% CI, 0.22–0.69) and death (HR, 0.42; 95% CI, 0.21-0.86). Also favoring TMMR, absolute difference in the risk of recurrence at 5 years was 9.4% (95% CI 3.2–15.7). In addition, 5-year OS was better in the TMMR group, at 93.3%, compared with 90.3% for standard treatment (P = .034).

Among patients with locally advanced disease, no significant differences in RFS or OS were observed.
 

Are these data strong enough to make TMMR the new standard treatment?

Dr. Falconer and colleagues concluded that TMMR with tLND “may replace the standard treatment approach in early-stage cervical cancer and furthermore be evaluated as an option in locally advanced cervical cancer confined to the Müllerian compartment.”

While the investigators anticipated demands for randomized controlled trials, they questioned the value of such studies, suggesting that any control arm would be “based on inconsistent or flawed concepts.”

How does TMMR fit into the current treatment landscape for cervical cancer?

“This is a very niche surgery that most places don’t do,” Dr. Modesitt said.

She pointed out that “multiple variations” on the standard radical hysterectomy have been proposed in the past, such as the laterally extended endopelvic resection.

“[TMMR] is not a new concept,” she said. “It’s just a question of how radical it is.”

Instead of developing new types of radical surgery, she said, the trend in the United States is toward de-escalation of surgical treatments altogether, with greater reliance upon medical options, such as immunotherapy.

“[This study] is thought provoking, and I applaud them for doing it,” Dr. Modesitt said. “But I’m not going to go out and do that on my next patient.”

This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden). Dr. Falconer is a board member of Surgical Science.

In the war against cancer, doctors and patients have long reached for three main weapons to target diseased cells: chemotherapy, radiation, and surgery.

But new research published this month in the journal Nature Materials suggests that manipulating the tissue around those cells — a strategy known as “mechanotherapeutics” — could play a critical role in reducing drug resistance and improving survival rates for hard-to-treat cancers like pancreatic cancer.

“Our study shows the importance of the tumor microenvironment and its properties in dictating how cancer progresses and responds to drug treatment,” said first author Bauer LeSavage, PhD, who conducted the study as a postdoctoral researcher in the Bioengineering Department at Stanford University, Stanford, California. “It also demonstrates that chemoresistance can be reversed.”

Each year, about 66,000 people are diagnosed with pancreatic cancer, and 52,000 die from it. It is a particularly lethal type of cancer, with 5-year survival rates hovering around 7% — a rate that has not improved much since 1996 when the first-line chemotherapy drug gemcitabine was approved.

It looks different from many cancers, said Lynn Matrisian, PhD, chief science officer for the nonprofit Pancreatic Cancer Action Network. Instead of a tumorous mass, it is made of islands of cancer cells surrounded by unusually dense fibrous tissue known as the extracellular matrix, which can collapse blood vessels and prevent drugs from reaching the tumor.

For the study, Dr. LeSavage and his team engineered synthetic but lifelike three-dimensional pancreas tissue with varying degrees of stiffness and different biochemical properties. Then they inserted bits of real tumors from patients with pancreatic cancer, watched them grow, and tried to kill them with drugs.

They found that cells growing in a stiff matrix were more resistant to chemotherapy than those growing in a softer matrix. But the story didn’t end there.

They also found that high amounts of the tissue-strengthening protein hyaluronic acid in stiff tissue seemed to signal the cancer cells to develop tiny pumps on their surface which shuttled out the drugs before they could take effect.

When the researchers moved the cancer cells into either a softer matrix or a stiff matrix in which the hyaluronic acid receptor, called CD44, was blocked, the chemotherapy drugs started working again.

“This suggests that if we can disrupt the stiffness signaling that’s happening through the CD44 receptor, we could make patients’ pancreatic cancer treatable again by normal chemotherapy,” said senior study author Sarah Heilshorn, PhD, a professor of materials science and engineering at Stanford. “These results suggest an exciting new direction for new drug development.”
 

Targeting Nearby Tissue: A Novel Approach to Fighting Chemoresistance

The study is not the first to suggest that chemically targeting the microenvironment surrounding a tumor can influence how patients respond to treatment.

In one recent clinical trial, patients with metastatic pancreatic cancer were given an experimental drug to inhibit a protein called connective tissue growth factor, reduce fibrous tissue, and make pancreatic tumors easier to surgically remove. Results have not been published yet.

Other research suggests that the generic blood pressure drug losartan, when given in combination with chemotherapy and radiation, can boost survival in patients with advanced pancreatic cancer by, in part, improving the health of blood vessels that carry drugs to the tumor.

But other studies of such mechanotherapeutics have yielded inconclusive results, said Dr. Matrisian.

“This paper points to another reason why we should not give up on this approach,” she said.

Ning Wang, PhD, director of the new Institute for Mechanobiology at Northeastern University College of Engineering, Boston, said there is no question that the composition of a tumor’s environment can influence how cancer progresses or responds to drugs. The new paper, he said, adds an important new chapter to the evolving story.

“But it’s very complicated. It’s not as simple as saying make it softer or stiffer and you can change the outcome for the patient,” Dr. Wang said.

In fact, some research has shown that tissue becomes stiffer when cancer arises so it can contain it from spreading.

In one animal study of pancreatic cancer that had spread to the liver, administering drugs to soften the surrounding tissue, or stroma, actually had the opposite effect — accelerating tumor growth and reducing survival rates.

Dr. Wang also noted that any drug designed to influence the extracellular matrix would need to be extremely localized, to prevent damage to other tissues, like bone or heart muscle.

Dr. LeSavage said he sees the paper as a case study in how important the extracellular matrix is and an example of how artificially grown organs or tissues can play a key role in testing how drugs work or don’t work.

He imagines a day when doctors could personalize treatments by taking a bit of a patient’s tumor, growing it in artificial tissue, and seeing how different tissue-altering drugs affect different therapies.

“This isn’t something that is just unique to pancreatic cancer,” he said, noting that the extracellular matrix throughout the body interacts with different cancers. “If we could take someone who has a chemoresistant tumor and convert it into something that is sensitive to existing therapies again, we could give them a second chance.”

A version of this article appeared on Medscape.com.

In the war against cancer, doctors and patients have long reached for three main weapons to target diseased cells: chemotherapy, radiation, and surgery.

But new research published this month in the journal Nature Materials suggests that manipulating the tissue around those cells — a strategy known as “mechanotherapeutics” — could play a critical role in reducing drug resistance and improving survival rates for hard-to-treat cancers like pancreatic cancer.

“Our study shows the importance of the tumor microenvironment and its properties in dictating how cancer progresses and responds to drug treatment,” said first author Bauer LeSavage, PhD, who conducted the study as a postdoctoral researcher in the Bioengineering Department at Stanford University, Stanford, California. “It also demonstrates that chemoresistance can be reversed.”

Each year, about 66,000 people are diagnosed with pancreatic cancer, and 52,000 die from it. It is a particularly lethal type of cancer, with 5-year survival rates hovering around 7% — a rate that has not improved much since 1996 when the first-line chemotherapy drug gemcitabine was approved.

It looks different from many cancers, said Lynn Matrisian, PhD, chief science officer for the nonprofit Pancreatic Cancer Action Network. Instead of a tumorous mass, it is made of islands of cancer cells surrounded by unusually dense fibrous tissue known as the extracellular matrix, which can collapse blood vessels and prevent drugs from reaching the tumor.

For the study, Dr. LeSavage and his team engineered synthetic but lifelike three-dimensional pancreas tissue with varying degrees of stiffness and different biochemical properties. Then they inserted bits of real tumors from patients with pancreatic cancer, watched them grow, and tried to kill them with drugs.

They found that cells growing in a stiff matrix were more resistant to chemotherapy than those growing in a softer matrix. But the story didn’t end there.

They also found that high amounts of the tissue-strengthening protein hyaluronic acid in stiff tissue seemed to signal the cancer cells to develop tiny pumps on their surface which shuttled out the drugs before they could take effect.

When the researchers moved the cancer cells into either a softer matrix or a stiff matrix in which the hyaluronic acid receptor, called CD44, was blocked, the chemotherapy drugs started working again.

“This suggests that if we can disrupt the stiffness signaling that’s happening through the CD44 receptor, we could make patients’ pancreatic cancer treatable again by normal chemotherapy,” said senior study author Sarah Heilshorn, PhD, a professor of materials science and engineering at Stanford. “These results suggest an exciting new direction for new drug development.”
 

Targeting Nearby Tissue: A Novel Approach to Fighting Chemoresistance

The study is not the first to suggest that chemically targeting the microenvironment surrounding a tumor can influence how patients respond to treatment.

In one recent clinical trial, patients with metastatic pancreatic cancer were given an experimental drug to inhibit a protein called connective tissue growth factor, reduce fibrous tissue, and make pancreatic tumors easier to surgically remove. Results have not been published yet.

Other research suggests that the generic blood pressure drug losartan, when given in combination with chemotherapy and radiation, can boost survival in patients with advanced pancreatic cancer by, in part, improving the health of blood vessels that carry drugs to the tumor.

But other studies of such mechanotherapeutics have yielded inconclusive results, said Dr. Matrisian.

“This paper points to another reason why we should not give up on this approach,” she said.

Ning Wang, PhD, director of the new Institute for Mechanobiology at Northeastern University College of Engineering, Boston, said there is no question that the composition of a tumor’s environment can influence how cancer progresses or responds to drugs. The new paper, he said, adds an important new chapter to the evolving story.

“But it’s very complicated. It’s not as simple as saying make it softer or stiffer and you can change the outcome for the patient,” Dr. Wang said.

In fact, some research has shown that tissue becomes stiffer when cancer arises so it can contain it from spreading.

In one animal study of pancreatic cancer that had spread to the liver, administering drugs to soften the surrounding tissue, or stroma, actually had the opposite effect — accelerating tumor growth and reducing survival rates.

Dr. Wang also noted that any drug designed to influence the extracellular matrix would need to be extremely localized, to prevent damage to other tissues, like bone or heart muscle.

Dr. LeSavage said he sees the paper as a case study in how important the extracellular matrix is and an example of how artificially grown organs or tissues can play a key role in testing how drugs work or don’t work.

He imagines a day when doctors could personalize treatments by taking a bit of a patient’s tumor, growing it in artificial tissue, and seeing how different tissue-altering drugs affect different therapies.

“This isn’t something that is just unique to pancreatic cancer,” he said, noting that the extracellular matrix throughout the body interacts with different cancers. “If we could take someone who has a chemoresistant tumor and convert it into something that is sensitive to existing therapies again, we could give them a second chance.”

A version of this article appeared on Medscape.com.

In the war against cancer, doctors and patients have long reached for three main weapons to target diseased cells: chemotherapy, radiation, and surgery.

But new research published this month in the journal Nature Materials suggests that manipulating the tissue around those cells — a strategy known as “mechanotherapeutics” — could play a critical role in reducing drug resistance and improving survival rates for hard-to-treat cancers like pancreatic cancer.

“Our study shows the importance of the tumor microenvironment and its properties in dictating how cancer progresses and responds to drug treatment,” said first author Bauer LeSavage, PhD, who conducted the study as a postdoctoral researcher in the Bioengineering Department at Stanford University, Stanford, California. “It also demonstrates that chemoresistance can be reversed.”

Each year, about 66,000 people are diagnosed with pancreatic cancer, and 52,000 die from it. It is a particularly lethal type of cancer, with 5-year survival rates hovering around 7% — a rate that has not improved much since 1996 when the first-line chemotherapy drug gemcitabine was approved.

It looks different from many cancers, said Lynn Matrisian, PhD, chief science officer for the nonprofit Pancreatic Cancer Action Network. Instead of a tumorous mass, it is made of islands of cancer cells surrounded by unusually dense fibrous tissue known as the extracellular matrix, which can collapse blood vessels and prevent drugs from reaching the tumor.

For the study, Dr. LeSavage and his team engineered synthetic but lifelike three-dimensional pancreas tissue with varying degrees of stiffness and different biochemical properties. Then they inserted bits of real tumors from patients with pancreatic cancer, watched them grow, and tried to kill them with drugs.

They found that cells growing in a stiff matrix were more resistant to chemotherapy than those growing in a softer matrix. But the story didn’t end there.

They also found that high amounts of the tissue-strengthening protein hyaluronic acid in stiff tissue seemed to signal the cancer cells to develop tiny pumps on their surface which shuttled out the drugs before they could take effect.

When the researchers moved the cancer cells into either a softer matrix or a stiff matrix in which the hyaluronic acid receptor, called CD44, was blocked, the chemotherapy drugs started working again.

“This suggests that if we can disrupt the stiffness signaling that’s happening through the CD44 receptor, we could make patients’ pancreatic cancer treatable again by normal chemotherapy,” said senior study author Sarah Heilshorn, PhD, a professor of materials science and engineering at Stanford. “These results suggest an exciting new direction for new drug development.”
 

Targeting Nearby Tissue: A Novel Approach to Fighting Chemoresistance

The study is not the first to suggest that chemically targeting the microenvironment surrounding a tumor can influence how patients respond to treatment.

In one recent clinical trial, patients with metastatic pancreatic cancer were given an experimental drug to inhibit a protein called connective tissue growth factor, reduce fibrous tissue, and make pancreatic tumors easier to surgically remove. Results have not been published yet.

Other research suggests that the generic blood pressure drug losartan, when given in combination with chemotherapy and radiation, can boost survival in patients with advanced pancreatic cancer by, in part, improving the health of blood vessels that carry drugs to the tumor.

But other studies of such mechanotherapeutics have yielded inconclusive results, said Dr. Matrisian.

“This paper points to another reason why we should not give up on this approach,” she said.

Ning Wang, PhD, director of the new Institute for Mechanobiology at Northeastern University College of Engineering, Boston, said there is no question that the composition of a tumor’s environment can influence how cancer progresses or responds to drugs. The new paper, he said, adds an important new chapter to the evolving story.

“But it’s very complicated. It’s not as simple as saying make it softer or stiffer and you can change the outcome for the patient,” Dr. Wang said.

In fact, some research has shown that tissue becomes stiffer when cancer arises so it can contain it from spreading.

In one animal study of pancreatic cancer that had spread to the liver, administering drugs to soften the surrounding tissue, or stroma, actually had the opposite effect — accelerating tumor growth and reducing survival rates.

Dr. Wang also noted that any drug designed to influence the extracellular matrix would need to be extremely localized, to prevent damage to other tissues, like bone or heart muscle.

Dr. LeSavage said he sees the paper as a case study in how important the extracellular matrix is and an example of how artificially grown organs or tissues can play a key role in testing how drugs work or don’t work.

He imagines a day when doctors could personalize treatments by taking a bit of a patient’s tumor, growing it in artificial tissue, and seeing how different tissue-altering drugs affect different therapies.

“This isn’t something that is just unique to pancreatic cancer,” he said, noting that the extracellular matrix throughout the body interacts with different cancers. “If we could take someone who has a chemoresistant tumor and convert it into something that is sensitive to existing therapies again, we could give them a second chance.”

A version of this article appeared on Medscape.com.

TOPLINE:

Surveillance of high-risk individuals may detect pancreatic ductal adenocarcinoma at an earlier stage, when the tumor is smaller and easier to treat, and could help improve survival in this population.

METHODOLOGY:

• Pancreatic ductal adenocarcinoma has poor 5-year survival rates and is often detected at later stages. General population screening is not recommended, but high-risk individuals, such as those with familial or genetic predispositions, may benefit from regular surveillance.
• The Cancer of the Pancreas Screening (CAPS) program, initiated in 1998, has been evaluating the effectiveness of such targeted surveillance for over two decades, but whether targeted surveillance confers a survival benefit remains unclear.
• The current study evaluated 26 high-risk individuals in the CAPS program who were ultimately diagnosed with pancreatic ductal adenocarcinoma. These high-risk individuals had undergone surveillance with annual endoscopic ultrasonography or MRI prior to diagnosis.
• The researchers compared these 26 individuals with 1504 matched control patients with pancreatic ductal adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database. The high-risk individuals and SEER control patients were matched on age, sex, and year of diagnosis.
• The primary outcomes were tumor stage at diagnosis, overall survival, and pancreatic cancer-specific mortality.

TAKEAWAY:

• High-risk individuals were significantly more likely to be diagnosed with early-stage pancreatic cancer: 38.5% were diagnosed at stage I vs 10.3% in the general US population, and 30.8% were diagnosed at stage II vs 25.1% in the general US population (P < .001).
• The median tumor size at diagnosis was smaller in high-risk individuals than in control patients (2.5 vs 3.6 cm; P < .001), and significantly fewer high-risk individuals had distant metastases at diagnosis (M1 stage) vs control patients (26.9% vs 53.8%; P = .01).
• Overall, high-risk individuals lived about 4.5 years longer — median of 61.7 months vs 8 months for control patients (hazard ratio [HR], 4.19; P < .001). In the 20 high-risk patients with screen-detected cancer, median overall survival was even higher at 144 months.
• The probability of surviving 5 years was significantly better in the high-risk group (50%) than in the control group (9%). And at 5 years, high-risk individuals had a significantly lower probability of dying from pancreatic cancer (HR, 3.58; P < .001).

IN PRACTICE:

Surveillance of high-risk individuals led to detection of “smaller pancreatic cancers, a greater number of patients with stage I disease,” as well as “a much higher likelihood of long-term survival than unscreened patients in the general population,” the authors concluded. “These findings suggest that selective surveillance of individuals at high risk for pancreatic cancer may improve clinical outcomes.”

SOURCE:

This study, with first author Amanda L. Blackford, from Johns Hopkins Medical Institutions, Baltimore, was published online July 3 in JAMA Oncology.

LIMITATIONS:

The findings might have limited generalizability due to enrollment at academic referral centers, limited racial and ethnic diversity, and a small number of high-risk individuals progressing to pancreatic cancer. The study also lacked a control group of unscreened high-risk individuals.

DISCLOSURES:

This study was supported by the National Institutes of Health, Susan Wojcicki and Dennis Troper, and others. Several authors reported financial ties outside this work.

A version of this article appeared on Medscape.com.

TOPLINE:

Surveillance of high-risk individuals may detect pancreatic ductal adenocarcinoma at an earlier stage, when the tumor is smaller and easier to treat, and could help improve survival in this population.

METHODOLOGY:

• Pancreatic ductal adenocarcinoma has poor 5-year survival rates and is often detected at later stages. General population screening is not recommended, but high-risk individuals, such as those with familial or genetic predispositions, may benefit from regular surveillance.
• The Cancer of the Pancreas Screening (CAPS) program, initiated in 1998, has been evaluating the effectiveness of such targeted surveillance for over two decades, but whether targeted surveillance confers a survival benefit remains unclear.
• The current study evaluated 26 high-risk individuals in the CAPS program who were ultimately diagnosed with pancreatic ductal adenocarcinoma. These high-risk individuals had undergone surveillance with annual endoscopic ultrasonography or MRI prior to diagnosis.
• The researchers compared these 26 individuals with 1504 matched control patients with pancreatic ductal adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database. The high-risk individuals and SEER control patients were matched on age, sex, and year of diagnosis.
• The primary outcomes were tumor stage at diagnosis, overall survival, and pancreatic cancer-specific mortality.

TAKEAWAY:

• High-risk individuals were significantly more likely to be diagnosed with early-stage pancreatic cancer: 38.5% were diagnosed at stage I vs 10.3% in the general US population, and 30.8% were diagnosed at stage II vs 25.1% in the general US population (P < .001).
• The median tumor size at diagnosis was smaller in high-risk individuals than in control patients (2.5 vs 3.6 cm; P < .001), and significantly fewer high-risk individuals had distant metastases at diagnosis (M1 stage) vs control patients (26.9% vs 53.8%; P = .01).
• Overall, high-risk individuals lived about 4.5 years longer — median of 61.7 months vs 8 months for control patients (hazard ratio [HR], 4.19; P < .001). In the 20 high-risk patients with screen-detected cancer, median overall survival was even higher at 144 months.
• The probability of surviving 5 years was significantly better in the high-risk group (50%) than in the control group (9%). And at 5 years, high-risk individuals had a significantly lower probability of dying from pancreatic cancer (HR, 3.58; P < .001).

IN PRACTICE:

Surveillance of high-risk individuals led to detection of “smaller pancreatic cancers, a greater number of patients with stage I disease,” as well as “a much higher likelihood of long-term survival than unscreened patients in the general population,” the authors concluded. “These findings suggest that selective surveillance of individuals at high risk for pancreatic cancer may improve clinical outcomes.”

SOURCE:

This study, with first author Amanda L. Blackford, from Johns Hopkins Medical Institutions, Baltimore, was published online July 3 in JAMA Oncology.

LIMITATIONS:

The findings might have limited generalizability due to enrollment at academic referral centers, limited racial and ethnic diversity, and a small number of high-risk individuals progressing to pancreatic cancer. The study also lacked a control group of unscreened high-risk individuals.

DISCLOSURES:

This study was supported by the National Institutes of Health, Susan Wojcicki and Dennis Troper, and others. Several authors reported financial ties outside this work.

A version of this article appeared on Medscape.com.

TOPLINE:

Surveillance of high-risk individuals may detect pancreatic ductal adenocarcinoma at an earlier stage, when the tumor is smaller and easier to treat, and could help improve survival in this population.

METHODOLOGY:

• Pancreatic ductal adenocarcinoma has poor 5-year survival rates and is often detected at later stages. General population screening is not recommended, but high-risk individuals, such as those with familial or genetic predispositions, may benefit from regular surveillance.
• The Cancer of the Pancreas Screening (CAPS) program, initiated in 1998, has been evaluating the effectiveness of such targeted surveillance for over two decades, but whether targeted surveillance confers a survival benefit remains unclear.
• The current study evaluated 26 high-risk individuals in the CAPS program who were ultimately diagnosed with pancreatic ductal adenocarcinoma. These high-risk individuals had undergone surveillance with annual endoscopic ultrasonography or MRI prior to diagnosis.
• The researchers compared these 26 individuals with 1504 matched control patients with pancreatic ductal adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database. The high-risk individuals and SEER control patients were matched on age, sex, and year of diagnosis.
• The primary outcomes were tumor stage at diagnosis, overall survival, and pancreatic cancer-specific mortality.

TAKEAWAY:

• High-risk individuals were significantly more likely to be diagnosed with early-stage pancreatic cancer: 38.5% were diagnosed at stage I vs 10.3% in the general US population, and 30.8% were diagnosed at stage II vs 25.1% in the general US population (P < .001).
• The median tumor size at diagnosis was smaller in high-risk individuals than in control patients (2.5 vs 3.6 cm; P < .001), and significantly fewer high-risk individuals had distant metastases at diagnosis (M1 stage) vs control patients (26.9% vs 53.8%; P = .01).
• Overall, high-risk individuals lived about 4.5 years longer — median of 61.7 months vs 8 months for control patients (hazard ratio [HR], 4.19; P < .001). In the 20 high-risk patients with screen-detected cancer, median overall survival was even higher at 144 months.
• The probability of surviving 5 years was significantly better in the high-risk group (50%) than in the control group (9%). And at 5 years, high-risk individuals had a significantly lower probability of dying from pancreatic cancer (HR, 3.58; P < .001).

IN PRACTICE:

Surveillance of high-risk individuals led to detection of “smaller pancreatic cancers, a greater number of patients with stage I disease,” as well as “a much higher likelihood of long-term survival than unscreened patients in the general population,” the authors concluded. “These findings suggest that selective surveillance of individuals at high risk for pancreatic cancer may improve clinical outcomes.”

SOURCE:

This study, with first author Amanda L. Blackford, from Johns Hopkins Medical Institutions, Baltimore, was published online July 3 in JAMA Oncology.

LIMITATIONS:

The findings might have limited generalizability due to enrollment at academic referral centers, limited racial and ethnic diversity, and a small number of high-risk individuals progressing to pancreatic cancer. The study also lacked a control group of unscreened high-risk individuals.

DISCLOSURES:

This study was supported by the National Institutes of Health, Susan Wojcicki and Dennis Troper, and others. Several authors reported financial ties outside this work.

A version of this article appeared on Medscape.com.

An electronic health record (EHR)–based nudge intervention could reduce potentially unnecessary sentinel lymph node biopsies (SLNB) among older women with early-stage breast cancer, the authors of new research say.

Participating surgeons noted that the reminder system added minimal friction to their workflow, as it did not require additional clicks or actions on the day of the patient visit, reported lead author Neil Carleton, PhD, of UPMC Hillman Cancer Center, Pittsburgh, and colleagues in JAMA Surgery (JAMA Surg. 2024 Jul 17. doi: 10.1001/jamasurg.2024.2407).

This effort to reduce the rate of SLNB stems from the Choosing Wisely campaign, which recommends against axillary staging in women 70 years and older with early-stage, clinically node-negative (cN0), hormone receptor–positive (HR+) breast cancer, the investigators said.

“These recommendations were developed because axillary staging did not impact survival, and rates of SLN positivity were low because of the tumor’s biological phenotype,” they wrote. “Even in older patients with tumors that exhibit concerning clinicopathologic features, limited nodal involvement does not often alter receipt of chemotherapy independently from genomic testing. Despite these recommendations, most women still receive axillary surgery.”
 

How Did the Nudge System Aim to Reduce the Rate of SLNB?

The nudge intervention involved adding a new column to the Epic schedule view, which flagged eligible patients during their first outpatient surgical consultation. The flag appeared as a caution sign or red clipboard icon. When surgeons hovered over the icon, a text box appeared, reminding them to consider omitting SLNB after a detailed review of core biopsy pathology and ultrasonographic imaging.

The intervention was evaluated at eight outpatient clinics within an integrated healthcare system that included seven breast surgical oncologists.

The study began with a 12-month preintervention period to serve as a control, during which time SLNB rate was determined via 194 patients in the target demographic. SLNB rate was again collected during the 12-month intervention period, which involved 193 patients meeting enrollment criteria. Between these periods, the investigators conducted a brief session lasting less than 30 minutes to introduce the surgeons to the rationale and design of the nudge column.
 

How Effective Was the Nudge System?

The intervention reduced the SLNB rate from 46.9% to 23.8%, representing a 49.3% decrease in use of SLNB. Efficacy was further supported by a significant reduction in SLNB according to an interrupted time series model (adjusted odds ratio, 0.26; 95% confidence interval, 0.07 to 0.90; P = .03). Extended follow-up showed that this effect was durable beyond the intervention period, with a 6-month mean reduction in SLNB of 15.6%.

Omission of SLNB led to higher rates of pathological node positivity during the intervention period (15.2% vs 8.8%), with all positive cases staged as pN1. Adjuvant therapy recommendations were similar between groups and driven by genomic testing, not nodal status. The intervention period also saw a decrease in referrals for lymphedema evaluation (3.6% vs. 6.2%).

How Might the Nudge System Be Implemented in Other Practices?

Although the SLNB nudge system was effective in the present study, likelihood of uptake among practices could vary widely, according to Anne M. Wallace, MD, professor of clinical surgery at UC San Diego Health and director of the Moores Comprehensive Breast Health Program.

On a fundamental level, not all centers use Epic software, which could present issues with compatibility, Dr. Wallace said in an interview. More importantly, she added, many institutions already have EHR-based alerts and reminders in place, so it is not always feasible to add a new nudge for every possible clinical scenario.

“Already there are so many little icons that we have to go through now when we close a note,” she said. “That’s why electronic medical records are becoming one of the leading stressors in medicine.”

This presents a more complex challenge, Dr. Wallace said, particularly as potentially practice-changing data are becoming available, and physicians may not have time to learn about them and integrate them into routine practice. She suggested that the present system may be most appropriate for oncologists in solo practice, or in small group practices where it is more challenging to have routine conversations about changing standards of care.

What Are the Risks of Using the Nudge System?

One of those conversations may surround the validity of the recommendation implemented in the present study.

Although the Society of Surgical Oncology recommends against SLNB in the described demographic, other experts, including Dr. Wallace, take a more nuanced view of the decision.

She noted that some patients with a chronological age of 70 may have a lower biological age, casting doubt on the legitimacy of the age threshold, and those near the threshold may wish to make the decision about staging for themselves.

Beyond these concerns, Dr. Wallace described two potential risks involved in forgoing SLNB.

First, there’s the potential for underestimating the tumor’s severity, she said, as this could mean a trip back to the operating room. A tumor initially thought to be low-grade might later be found to be high-grade, necessitating further surgery. Some patients might refuse additional surgery, leaving the more aggressive tumor untreated.

Second, the nudge system could complicate radiation treatment decisions, Dr. Wallace said. Without full nodal status, some radiation oncologists might push for additional radiation therapy, which incurs a greater treatment burden than SNLB.
 

What Are Some Alternatives to the Nudge System?

After discussing the strengths and weaknesses of the present EHR-based nudge system, and others like it, Dr. Wallace returned to the importance of ongoing communication among colleagues managing complex cases.

At UC San Diego Health, where oncologists meet weekly for a 2-hour breast cancer conference, “we nudge each other,” she said.

This study was supported by the Shear Family Foundation, UPMC eRecord Ambulatory Decision Support and Analytics, UPMC Hillman Cancer Center Biostatistics Facility, and National Institutes of Health. The investigators disclosed relationships with Pfizer, Amgen, the Lewin Group, and Milestone Pennsylvania, and others.

An electronic health record (EHR)–based nudge intervention could reduce potentially unnecessary sentinel lymph node biopsies (SLNB) among older women with early-stage breast cancer, the authors of new research say.

Participating surgeons noted that the reminder system added minimal friction to their workflow, as it did not require additional clicks or actions on the day of the patient visit, reported lead author Neil Carleton, PhD, of UPMC Hillman Cancer Center, Pittsburgh, and colleagues in JAMA Surgery (JAMA Surg. 2024 Jul 17. doi: 10.1001/jamasurg.2024.2407).

This effort to reduce the rate of SLNB stems from the Choosing Wisely campaign, which recommends against axillary staging in women 70 years and older with early-stage, clinically node-negative (cN0), hormone receptor–positive (HR+) breast cancer, the investigators said.

“These recommendations were developed because axillary staging did not impact survival, and rates of SLN positivity were low because of the tumor’s biological phenotype,” they wrote. “Even in older patients with tumors that exhibit concerning clinicopathologic features, limited nodal involvement does not often alter receipt of chemotherapy independently from genomic testing. Despite these recommendations, most women still receive axillary surgery.”
 

How Did the Nudge System Aim to Reduce the Rate of SLNB?

The nudge intervention involved adding a new column to the Epic schedule view, which flagged eligible patients during their first outpatient surgical consultation. The flag appeared as a caution sign or red clipboard icon. When surgeons hovered over the icon, a text box appeared, reminding them to consider omitting SLNB after a detailed review of core biopsy pathology and ultrasonographic imaging.

The intervention was evaluated at eight outpatient clinics within an integrated healthcare system that included seven breast surgical oncologists.

The study began with a 12-month preintervention period to serve as a control, during which time SLNB rate was determined via 194 patients in the target demographic. SLNB rate was again collected during the 12-month intervention period, which involved 193 patients meeting enrollment criteria. Between these periods, the investigators conducted a brief session lasting less than 30 minutes to introduce the surgeons to the rationale and design of the nudge column.
 

How Effective Was the Nudge System?

The intervention reduced the SLNB rate from 46.9% to 23.8%, representing a 49.3% decrease in use of SLNB. Efficacy was further supported by a significant reduction in SLNB according to an interrupted time series model (adjusted odds ratio, 0.26; 95% confidence interval, 0.07 to 0.90; P = .03). Extended follow-up showed that this effect was durable beyond the intervention period, with a 6-month mean reduction in SLNB of 15.6%.

Omission of SLNB led to higher rates of pathological node positivity during the intervention period (15.2% vs 8.8%), with all positive cases staged as pN1. Adjuvant therapy recommendations were similar between groups and driven by genomic testing, not nodal status. The intervention period also saw a decrease in referrals for lymphedema evaluation (3.6% vs. 6.2%).

How Might the Nudge System Be Implemented in Other Practices?

Although the SLNB nudge system was effective in the present study, likelihood of uptake among practices could vary widely, according to Anne M. Wallace, MD, professor of clinical surgery at UC San Diego Health and director of the Moores Comprehensive Breast Health Program.

On a fundamental level, not all centers use Epic software, which could present issues with compatibility, Dr. Wallace said in an interview. More importantly, she added, many institutions already have EHR-based alerts and reminders in place, so it is not always feasible to add a new nudge for every possible clinical scenario.

“Already there are so many little icons that we have to go through now when we close a note,” she said. “That’s why electronic medical records are becoming one of the leading stressors in medicine.”

This presents a more complex challenge, Dr. Wallace said, particularly as potentially practice-changing data are becoming available, and physicians may not have time to learn about them and integrate them into routine practice. She suggested that the present system may be most appropriate for oncologists in solo practice, or in small group practices where it is more challenging to have routine conversations about changing standards of care.

What Are the Risks of Using the Nudge System?

One of those conversations may surround the validity of the recommendation implemented in the present study.

Although the Society of Surgical Oncology recommends against SLNB in the described demographic, other experts, including Dr. Wallace, take a more nuanced view of the decision.

She noted that some patients with a chronological age of 70 may have a lower biological age, casting doubt on the legitimacy of the age threshold, and those near the threshold may wish to make the decision about staging for themselves.

Beyond these concerns, Dr. Wallace described two potential risks involved in forgoing SLNB.

First, there’s the potential for underestimating the tumor’s severity, she said, as this could mean a trip back to the operating room. A tumor initially thought to be low-grade might later be found to be high-grade, necessitating further surgery. Some patients might refuse additional surgery, leaving the more aggressive tumor untreated.

Second, the nudge system could complicate radiation treatment decisions, Dr. Wallace said. Without full nodal status, some radiation oncologists might push for additional radiation therapy, which incurs a greater treatment burden than SNLB.
 

What Are Some Alternatives to the Nudge System?

After discussing the strengths and weaknesses of the present EHR-based nudge system, and others like it, Dr. Wallace returned to the importance of ongoing communication among colleagues managing complex cases.

At UC San Diego Health, where oncologists meet weekly for a 2-hour breast cancer conference, “we nudge each other,” she said.

This study was supported by the Shear Family Foundation, UPMC eRecord Ambulatory Decision Support and Analytics, UPMC Hillman Cancer Center Biostatistics Facility, and National Institutes of Health. The investigators disclosed relationships with Pfizer, Amgen, the Lewin Group, and Milestone Pennsylvania, and others.

An electronic health record (EHR)–based nudge intervention could reduce potentially unnecessary sentinel lymph node biopsies (SLNB) among older women with early-stage breast cancer, the authors of new research say.

Participating surgeons noted that the reminder system added minimal friction to their workflow, as it did not require additional clicks or actions on the day of the patient visit, reported lead author Neil Carleton, PhD, of UPMC Hillman Cancer Center, Pittsburgh, and colleagues in JAMA Surgery (JAMA Surg. 2024 Jul 17. doi: 10.1001/jamasurg.2024.2407).

This effort to reduce the rate of SLNB stems from the Choosing Wisely campaign, which recommends against axillary staging in women 70 years and older with early-stage, clinically node-negative (cN0), hormone receptor–positive (HR+) breast cancer, the investigators said.

“These recommendations were developed because axillary staging did not impact survival, and rates of SLN positivity were low because of the tumor’s biological phenotype,” they wrote. “Even in older patients with tumors that exhibit concerning clinicopathologic features, limited nodal involvement does not often alter receipt of chemotherapy independently from genomic testing. Despite these recommendations, most women still receive axillary surgery.”
 

How Did the Nudge System Aim to Reduce the Rate of SLNB?

The nudge intervention involved adding a new column to the Epic schedule view, which flagged eligible patients during their first outpatient surgical consultation. The flag appeared as a caution sign or red clipboard icon. When surgeons hovered over the icon, a text box appeared, reminding them to consider omitting SLNB after a detailed review of core biopsy pathology and ultrasonographic imaging.

The intervention was evaluated at eight outpatient clinics within an integrated healthcare system that included seven breast surgical oncologists.

The study began with a 12-month preintervention period to serve as a control, during which time SLNB rate was determined via 194 patients in the target demographic. SLNB rate was again collected during the 12-month intervention period, which involved 193 patients meeting enrollment criteria. Between these periods, the investigators conducted a brief session lasting less than 30 minutes to introduce the surgeons to the rationale and design of the nudge column.
 

How Effective Was the Nudge System?

The intervention reduced the SLNB rate from 46.9% to 23.8%, representing a 49.3% decrease in use of SLNB. Efficacy was further supported by a significant reduction in SLNB according to an interrupted time series model (adjusted odds ratio, 0.26; 95% confidence interval, 0.07 to 0.90; P = .03). Extended follow-up showed that this effect was durable beyond the intervention period, with a 6-month mean reduction in SLNB of 15.6%.

Omission of SLNB led to higher rates of pathological node positivity during the intervention period (15.2% vs 8.8%), with all positive cases staged as pN1. Adjuvant therapy recommendations were similar between groups and driven by genomic testing, not nodal status. The intervention period also saw a decrease in referrals for lymphedema evaluation (3.6% vs. 6.2%).

How Might the Nudge System Be Implemented in Other Practices?

Although the SLNB nudge system was effective in the present study, likelihood of uptake among practices could vary widely, according to Anne M. Wallace, MD, professor of clinical surgery at UC San Diego Health and director of the Moores Comprehensive Breast Health Program.

On a fundamental level, not all centers use Epic software, which could present issues with compatibility, Dr. Wallace said in an interview. More importantly, she added, many institutions already have EHR-based alerts and reminders in place, so it is not always feasible to add a new nudge for every possible clinical scenario.

“Already there are so many little icons that we have to go through now when we close a note,” she said. “That’s why electronic medical records are becoming one of the leading stressors in medicine.”

This presents a more complex challenge, Dr. Wallace said, particularly as potentially practice-changing data are becoming available, and physicians may not have time to learn about them and integrate them into routine practice. She suggested that the present system may be most appropriate for oncologists in solo practice, or in small group practices where it is more challenging to have routine conversations about changing standards of care.

What Are the Risks of Using the Nudge System?

One of those conversations may surround the validity of the recommendation implemented in the present study.

Although the Society of Surgical Oncology recommends against SLNB in the described demographic, other experts, including Dr. Wallace, take a more nuanced view of the decision.

She noted that some patients with a chronological age of 70 may have a lower biological age, casting doubt on the legitimacy of the age threshold, and those near the threshold may wish to make the decision about staging for themselves.

Beyond these concerns, Dr. Wallace described two potential risks involved in forgoing SLNB.

First, there’s the potential for underestimating the tumor’s severity, she said, as this could mean a trip back to the operating room. A tumor initially thought to be low-grade might later be found to be high-grade, necessitating further surgery. Some patients might refuse additional surgery, leaving the more aggressive tumor untreated.

Second, the nudge system could complicate radiation treatment decisions, Dr. Wallace said. Without full nodal status, some radiation oncologists might push for additional radiation therapy, which incurs a greater treatment burden than SNLB.
 

What Are Some Alternatives to the Nudge System?

After discussing the strengths and weaknesses of the present EHR-based nudge system, and others like it, Dr. Wallace returned to the importance of ongoing communication among colleagues managing complex cases.

At UC San Diego Health, where oncologists meet weekly for a 2-hour breast cancer conference, “we nudge each other,” she said.

This study was supported by the Shear Family Foundation, UPMC eRecord Ambulatory Decision Support and Analytics, UPMC Hillman Cancer Center Biostatistics Facility, and National Institutes of Health. The investigators disclosed relationships with Pfizer, Amgen, the Lewin Group, and Milestone Pennsylvania, and others.

Patients starting first-line endocrine and CDK4/6 inhibition for advanced breast cancer show minimal additional cognitive decline beyond what they had already experienced from their neoadjuvant and adjuvant treatments, according to new results of the SONIA trial.

“Patients who are diagnosed with advanced breast cancer and start their first-line treatment already show cognitive impairments due to their previous treatments. And luckily, our results show that during first-line treatment for advanced breast cancer with endocrine therapy, with or without a CDK4/6 inhibitor, further cognitive decline is minimal,” lead investigator Maryse Luijendijk, said during her presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

“It is well known that cancer patients can experience cognitive problems, such as memory loss, problems with concentration or with planning, during or following their treatment,” explained Ms. Luijendijk, a PhD candidate in the department of Psychosocial Research and Epidemiology at the Netherlands Cancer Institute, in Amsterdam. “Much is known about the effects of chemotherapy or irradiation to the brain, but evidence into endocrine therapy is scarce, which is surprising because cognitive effects are biologically plausible.

“We know that estrogen plays an important role in neuronal functioning and that certain types of endocrine therapies are able to cross the blood-brain barrier, where they may interact with estrogen receptors distributed widely throughout the brain … We know that CDK4/6 inhibitors may either negatively affect cognitive function by increased fatigue due to cytokine release or by interrupting the cell cycle of healthy cells, or positively, as they have been associated with reduced inflammation and remyelination.”

Initial results of the SONIA trial, reported at ASCO last year, examined overall and progression-free survival in patients with HR-positive, HER2-negative metastatic breast cancer and no prior treatment for advanced disease. Findings for those who were randomized to treatment with nonsteroidal aromatase inhibition either with or without the addition of CDK4/6 inhibitors showed no between-group differences, explained Ms. Luijendijk.

The new results, described as being from the SONIA-EfFECT (Evaluation of cognitive functioning in patients with metastatic breast cancer treated with endocrine or combined therapy) trial, were based on the authors investigating cognitive functioning in the same cohort used in the SONIA trial plus a control group.

In SONIA-EfFECT, patients who participated in SONIA were asked to identify a female relative or friend without cancer to serve as a cancer-free control. Members of the 130-patient control group were matched for age, education, and computer use.

Participants in the SONIA trial and control group were asked to complete the Amsterdam Cognition Scan, an online neuropsychological test battery at baseline and again after 9 months of treatment. Of those patients from SONIA, 130 had received first-line treatment with aromatase inhibitors with CDK4/6 inhibition (Arm A) and 130 had received aromatase inhibitors without CDK4/6 inhibition (Arm B).

Baseline assessments for SONIA-EfFECT were completed for 260 patients from SONIA and the full 130-person control group. Follow-up assessments were completed for 119 members of the control group and 199 patients from the original SONIA trial (108 from Arm A, and 91 from Arm B). Patients from SONIA who switched to second-line treatment within 9 months were not retested.

Patients in both SONIA arms performed significantly worse than the controls on the domains of verbal memory, working memory, processing speed, executive function, and motor function. In both patient arms and the controls, standardized regression-based change scores showed limited decline in cognitive function over the 9-month interval. Minimal differences in cognitive change were observed between the patients treated with and without CDK4/6 inhibitors, and between patients and the controls, according to the abstract for SONIA-EfFECT, published in the program for the annual meeting of ASCO.

“At baseline, patients show worse cognitive function across all domains compared to the controls. And as expected, there were no differences between the two treatment arms,” Ms. Luijendijk explained. After 9 months of treatment, the testing showed limited further decline among patients, “and even some improvement on some tests,” with minimal differences between treatment arms “implying that cognitive function does not need to be an aspect when deciding on treatment.”

Ms. Luijendijk reported no relevant disclosures.

Patients starting first-line endocrine and CDK4/6 inhibition for advanced breast cancer show minimal additional cognitive decline beyond what they had already experienced from their neoadjuvant and adjuvant treatments, according to new results of the SONIA trial.

“Patients who are diagnosed with advanced breast cancer and start their first-line treatment already show cognitive impairments due to their previous treatments. And luckily, our results show that during first-line treatment for advanced breast cancer with endocrine therapy, with or without a CDK4/6 inhibitor, further cognitive decline is minimal,” lead investigator Maryse Luijendijk, said during her presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

“It is well known that cancer patients can experience cognitive problems, such as memory loss, problems with concentration or with planning, during or following their treatment,” explained Ms. Luijendijk, a PhD candidate in the department of Psychosocial Research and Epidemiology at the Netherlands Cancer Institute, in Amsterdam. “Much is known about the effects of chemotherapy or irradiation to the brain, but evidence into endocrine therapy is scarce, which is surprising because cognitive effects are biologically plausible.

“We know that estrogen plays an important role in neuronal functioning and that certain types of endocrine therapies are able to cross the blood-brain barrier, where they may interact with estrogen receptors distributed widely throughout the brain … We know that CDK4/6 inhibitors may either negatively affect cognitive function by increased fatigue due to cytokine release or by interrupting the cell cycle of healthy cells, or positively, as they have been associated with reduced inflammation and remyelination.”

Initial results of the SONIA trial, reported at ASCO last year, examined overall and progression-free survival in patients with HR-positive, HER2-negative metastatic breast cancer and no prior treatment for advanced disease. Findings for those who were randomized to treatment with nonsteroidal aromatase inhibition either with or without the addition of CDK4/6 inhibitors showed no between-group differences, explained Ms. Luijendijk.

The new results, described as being from the SONIA-EfFECT (Evaluation of cognitive functioning in patients with metastatic breast cancer treated with endocrine or combined therapy) trial, were based on the authors investigating cognitive functioning in the same cohort used in the SONIA trial plus a control group.

In SONIA-EfFECT, patients who participated in SONIA were asked to identify a female relative or friend without cancer to serve as a cancer-free control. Members of the 130-patient control group were matched for age, education, and computer use.

Participants in the SONIA trial and control group were asked to complete the Amsterdam Cognition Scan, an online neuropsychological test battery at baseline and again after 9 months of treatment. Of those patients from SONIA, 130 had received first-line treatment with aromatase inhibitors with CDK4/6 inhibition (Arm A) and 130 had received aromatase inhibitors without CDK4/6 inhibition (Arm B).

Baseline assessments for SONIA-EfFECT were completed for 260 patients from SONIA and the full 130-person control group. Follow-up assessments were completed for 119 members of the control group and 199 patients from the original SONIA trial (108 from Arm A, and 91 from Arm B). Patients from SONIA who switched to second-line treatment within 9 months were not retested.

Patients in both SONIA arms performed significantly worse than the controls on the domains of verbal memory, working memory, processing speed, executive function, and motor function. In both patient arms and the controls, standardized regression-based change scores showed limited decline in cognitive function over the 9-month interval. Minimal differences in cognitive change were observed between the patients treated with and without CDK4/6 inhibitors, and between patients and the controls, according to the abstract for SONIA-EfFECT, published in the program for the annual meeting of ASCO.

“At baseline, patients show worse cognitive function across all domains compared to the controls. And as expected, there were no differences between the two treatment arms,” Ms. Luijendijk explained. After 9 months of treatment, the testing showed limited further decline among patients, “and even some improvement on some tests,” with minimal differences between treatment arms “implying that cognitive function does not need to be an aspect when deciding on treatment.”

Ms. Luijendijk reported no relevant disclosures.

Patients starting first-line endocrine and CDK4/6 inhibition for advanced breast cancer show minimal additional cognitive decline beyond what they had already experienced from their neoadjuvant and adjuvant treatments, according to new results of the SONIA trial.

“Patients who are diagnosed with advanced breast cancer and start their first-line treatment already show cognitive impairments due to their previous treatments. And luckily, our results show that during first-line treatment for advanced breast cancer with endocrine therapy, with or without a CDK4/6 inhibitor, further cognitive decline is minimal,” lead investigator Maryse Luijendijk, said during her presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

“It is well known that cancer patients can experience cognitive problems, such as memory loss, problems with concentration or with planning, during or following their treatment,” explained Ms. Luijendijk, a PhD candidate in the department of Psychosocial Research and Epidemiology at the Netherlands Cancer Institute, in Amsterdam. “Much is known about the effects of chemotherapy or irradiation to the brain, but evidence into endocrine therapy is scarce, which is surprising because cognitive effects are biologically plausible.

“We know that estrogen plays an important role in neuronal functioning and that certain types of endocrine therapies are able to cross the blood-brain barrier, where they may interact with estrogen receptors distributed widely throughout the brain … We know that CDK4/6 inhibitors may either negatively affect cognitive function by increased fatigue due to cytokine release or by interrupting the cell cycle of healthy cells, or positively, as they have been associated with reduced inflammation and remyelination.”

Initial results of the SONIA trial, reported at ASCO last year, examined overall and progression-free survival in patients with HR-positive, HER2-negative metastatic breast cancer and no prior treatment for advanced disease. Findings for those who were randomized to treatment with nonsteroidal aromatase inhibition either with or without the addition of CDK4/6 inhibitors showed no between-group differences, explained Ms. Luijendijk.

The new results, described as being from the SONIA-EfFECT (Evaluation of cognitive functioning in patients with metastatic breast cancer treated with endocrine or combined therapy) trial, were based on the authors investigating cognitive functioning in the same cohort used in the SONIA trial plus a control group.

In SONIA-EfFECT, patients who participated in SONIA were asked to identify a female relative or friend without cancer to serve as a cancer-free control. Members of the 130-patient control group were matched for age, education, and computer use.

Participants in the SONIA trial and control group were asked to complete the Amsterdam Cognition Scan, an online neuropsychological test battery at baseline and again after 9 months of treatment. Of those patients from SONIA, 130 had received first-line treatment with aromatase inhibitors with CDK4/6 inhibition (Arm A) and 130 had received aromatase inhibitors without CDK4/6 inhibition (Arm B).

Baseline assessments for SONIA-EfFECT were completed for 260 patients from SONIA and the full 130-person control group. Follow-up assessments were completed for 119 members of the control group and 199 patients from the original SONIA trial (108 from Arm A, and 91 from Arm B). Patients from SONIA who switched to second-line treatment within 9 months were not retested.

Patients in both SONIA arms performed significantly worse than the controls on the domains of verbal memory, working memory, processing speed, executive function, and motor function. In both patient arms and the controls, standardized regression-based change scores showed limited decline in cognitive function over the 9-month interval. Minimal differences in cognitive change were observed between the patients treated with and without CDK4/6 inhibitors, and between patients and the controls, according to the abstract for SONIA-EfFECT, published in the program for the annual meeting of ASCO.

“At baseline, patients show worse cognitive function across all domains compared to the controls. And as expected, there were no differences between the two treatment arms,” Ms. Luijendijk explained. After 9 months of treatment, the testing showed limited further decline among patients, “and even some improvement on some tests,” with minimal differences between treatment arms “implying that cognitive function does not need to be an aspect when deciding on treatment.”

Ms. Luijendijk reported no relevant disclosures.