Oncology

The targeted therapy combination of encorafenib and cetuximab with FOLFIRI (leucovorin/5-fluorouracil [FU]/irinotecan) chemotherapy may be a new first-line option for patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), according to new results from the BREAKWATER trial.

After a median follow-up of about 10 months, response rates were significantly better with encorafenib and cetuximab plus FOLFIRI than with FOLFIRI alone — without increasing side effects.

The findings, presented at the ASCO Gastrointestinal Cancers Symposium 2026, point to a potential new option for the 20%-25% of patients with BRAF V600E-mutant metastatic CRC who receive FOLFIRI as their chemotherapy.

Based on previous results from BREAKWATER, the FDA granted accelerated approval to first-line encorafenib (Braftovi) and cetuximab (Erbitux) plus mFOLFOX6 for this patient population. That regimen doubled median overall survival compared with standard chemotherapy with or without bevacizumab.

Cohort 3 of BREAKWATER was designed to address a specific question: Are the benefits with the targeted therapy duo a “FOLFOX-specific phenomenon?” lead investigator Scott Kopetz, MD, PhD, of MD Anderson Cancer Center, Houston, said during a press briefing.

Based on these early results, the answer is no. Instead, Kopetz said, there appears to be a “broader synergy” between the targeted therapies and cytotoxic chemotherapy.

Joel Saltzman, MD, ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic in Cleveland, agreed.

“The additional data from the BREAKWATER trial reveals that it is the targeted therapy backbone that provides the better disease control and response rate in BRAF V600E-mutant colorectal cancers,” he said.

BRAF V600E mutations occur in up to 12% of patients with metastatic CRC and are associated with poor outcomes. While many newly diagnosed patients receive FOLFOX (leucovorin/5-FU/oxaliplatin) in the first line, FOLFIRI is a common alternative — often due to concerns about oxaliplatin-associated peripheral neuropathy, Kopetz noted.

The safety lead-in portion of BREAKWATER showed that encorafenib and cetuximab plus FOLFIRI were tolerable and had promising antitumor activity.

Cohort 3 of the trial included 147 patients (mean age, 62 years; 46% male) with BRAF V600E-mutant metastatic CRC, no prior systemic treatment, and good performance status (Eastern Cooperative Oncology Group PS 0 or 1); 73 patients were randomly allocated to encorafenib and cetuximab plus FOLFIRI and 74 to FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate assessed by blinded independent central review.

After a median follow-up of 10 months, patients in the targeted therapy group had an objective response rate of 64.4% vs 39.2% among patients who received FOLFIRI alone or with bevacizumab (odds ratio, 2.76; P = .001).

Responses to the targeted therapies were “rapid and durable,” Kopetz said. More than half (57.4%) of patients treated with encorafenib and cetuximab and FOLFIRI had a duration of response of 6 months or longer than 34.5% in the control group.

Data on overall survival, a secondary endpoint, were not yet mature, but there was a trend toward improved survival with targeted therapy.

Importantly, Kopetz reported, there were no new safety signals, and serious treatment-emergent adverse events occurred at a similar rate in both treatment groups: 39.4% in the targeted therapy group and 36.8% in the control group.

The most common adverse events in both groups included nausea, diarrhea, vomiting, fatigue, appetite loss, and alopecia. About 10% of patients in the targeted therapy group and 9% of those in the control group discontinued their treatment early, suggesting the severity of side effects was similar between the groups.

Kopetz cautioned that the data are still early and follow-up is ongoing. However, he said, the findings support the targeted drugs plus FOLFIRI as a “potential new standard of care” for this patient population.

“The addition of FOLFIRI chemotherapy in the frontline setting will give oncologists and patients more options when selecting a first-line regimen,” Saltzman said. “To have as many options as possible is certainly something we all hope for.”

The trial was funded by Pfizer. Kopetz reported consulting for Pfizer and several other pharmaceutical companies. Saltzman reported having no disclosures.

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

The targeted therapy combination of encorafenib and cetuximab with FOLFIRI (leucovorin/5-fluorouracil [FU]/irinotecan) chemotherapy may be a new first-line option for patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), according to new results from the BREAKWATER trial.

After a median follow-up of about 10 months, response rates were significantly better with encorafenib and cetuximab plus FOLFIRI than with FOLFIRI alone — without increasing side effects.

The findings, presented at the ASCO Gastrointestinal Cancers Symposium 2026, point to a potential new option for the 20%-25% of patients with BRAF V600E-mutant metastatic CRC who receive FOLFIRI as their chemotherapy.

Based on previous results from BREAKWATER, the FDA granted accelerated approval to first-line encorafenib (Braftovi) and cetuximab (Erbitux) plus mFOLFOX6 for this patient population. That regimen doubled median overall survival compared with standard chemotherapy with or without bevacizumab.

Cohort 3 of BREAKWATER was designed to address a specific question: Are the benefits with the targeted therapy duo a “FOLFOX-specific phenomenon?” lead investigator Scott Kopetz, MD, PhD, of MD Anderson Cancer Center, Houston, said during a press briefing.

Based on these early results, the answer is no. Instead, Kopetz said, there appears to be a “broader synergy” between the targeted therapies and cytotoxic chemotherapy.

Joel Saltzman, MD, ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic in Cleveland, agreed.

“The additional data from the BREAKWATER trial reveals that it is the targeted therapy backbone that provides the better disease control and response rate in BRAF V600E-mutant colorectal cancers,” he said.

BRAF V600E mutations occur in up to 12% of patients with metastatic CRC and are associated with poor outcomes. While many newly diagnosed patients receive FOLFOX (leucovorin/5-FU/oxaliplatin) in the first line, FOLFIRI is a common alternative — often due to concerns about oxaliplatin-associated peripheral neuropathy, Kopetz noted.

The safety lead-in portion of BREAKWATER showed that encorafenib and cetuximab plus FOLFIRI were tolerable and had promising antitumor activity.

Cohort 3 of the trial included 147 patients (mean age, 62 years; 46% male) with BRAF V600E-mutant metastatic CRC, no prior systemic treatment, and good performance status (Eastern Cooperative Oncology Group PS 0 or 1); 73 patients were randomly allocated to encorafenib and cetuximab plus FOLFIRI and 74 to FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate assessed by blinded independent central review.

After a median follow-up of 10 months, patients in the targeted therapy group had an objective response rate of 64.4% vs 39.2% among patients who received FOLFIRI alone or with bevacizumab (odds ratio, 2.76; P = .001).

Responses to the targeted therapies were “rapid and durable,” Kopetz said. More than half (57.4%) of patients treated with encorafenib and cetuximab and FOLFIRI had a duration of response of 6 months or longer than 34.5% in the control group.

Data on overall survival, a secondary endpoint, were not yet mature, but there was a trend toward improved survival with targeted therapy.

Importantly, Kopetz reported, there were no new safety signals, and serious treatment-emergent adverse events occurred at a similar rate in both treatment groups: 39.4% in the targeted therapy group and 36.8% in the control group.

The most common adverse events in both groups included nausea, diarrhea, vomiting, fatigue, appetite loss, and alopecia. About 10% of patients in the targeted therapy group and 9% of those in the control group discontinued their treatment early, suggesting the severity of side effects was similar between the groups.

Kopetz cautioned that the data are still early and follow-up is ongoing. However, he said, the findings support the targeted drugs plus FOLFIRI as a “potential new standard of care” for this patient population.

“The addition of FOLFIRI chemotherapy in the frontline setting will give oncologists and patients more options when selecting a first-line regimen,” Saltzman said. “To have as many options as possible is certainly something we all hope for.”

The trial was funded by Pfizer. Kopetz reported consulting for Pfizer and several other pharmaceutical companies. Saltzman reported having no disclosures.

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

The targeted therapy combination of encorafenib and cetuximab with FOLFIRI (leucovorin/5-fluorouracil [FU]/irinotecan) chemotherapy may be a new first-line option for patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), according to new results from the BREAKWATER trial.

After a median follow-up of about 10 months, response rates were significantly better with encorafenib and cetuximab plus FOLFIRI than with FOLFIRI alone — without increasing side effects.

The findings, presented at the ASCO Gastrointestinal Cancers Symposium 2026, point to a potential new option for the 20%-25% of patients with BRAF V600E-mutant metastatic CRC who receive FOLFIRI as their chemotherapy.

Based on previous results from BREAKWATER, the FDA granted accelerated approval to first-line encorafenib (Braftovi) and cetuximab (Erbitux) plus mFOLFOX6 for this patient population. That regimen doubled median overall survival compared with standard chemotherapy with or without bevacizumab.

Cohort 3 of BREAKWATER was designed to address a specific question: Are the benefits with the targeted therapy duo a “FOLFOX-specific phenomenon?” lead investigator Scott Kopetz, MD, PhD, of MD Anderson Cancer Center, Houston, said during a press briefing.

Based on these early results, the answer is no. Instead, Kopetz said, there appears to be a “broader synergy” between the targeted therapies and cytotoxic chemotherapy.

Joel Saltzman, MD, ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic in Cleveland, agreed.

“The additional data from the BREAKWATER trial reveals that it is the targeted therapy backbone that provides the better disease control and response rate in BRAF V600E-mutant colorectal cancers,” he said.

BRAF V600E mutations occur in up to 12% of patients with metastatic CRC and are associated with poor outcomes. While many newly diagnosed patients receive FOLFOX (leucovorin/5-FU/oxaliplatin) in the first line, FOLFIRI is a common alternative — often due to concerns about oxaliplatin-associated peripheral neuropathy, Kopetz noted.

The safety lead-in portion of BREAKWATER showed that encorafenib and cetuximab plus FOLFIRI were tolerable and had promising antitumor activity.

Cohort 3 of the trial included 147 patients (mean age, 62 years; 46% male) with BRAF V600E-mutant metastatic CRC, no prior systemic treatment, and good performance status (Eastern Cooperative Oncology Group PS 0 or 1); 73 patients were randomly allocated to encorafenib and cetuximab plus FOLFIRI and 74 to FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate assessed by blinded independent central review.

After a median follow-up of 10 months, patients in the targeted therapy group had an objective response rate of 64.4% vs 39.2% among patients who received FOLFIRI alone or with bevacizumab (odds ratio, 2.76; P = .001).

Responses to the targeted therapies were “rapid and durable,” Kopetz said. More than half (57.4%) of patients treated with encorafenib and cetuximab and FOLFIRI had a duration of response of 6 months or longer than 34.5% in the control group.

Data on overall survival, a secondary endpoint, were not yet mature, but there was a trend toward improved survival with targeted therapy.

Importantly, Kopetz reported, there were no new safety signals, and serious treatment-emergent adverse events occurred at a similar rate in both treatment groups: 39.4% in the targeted therapy group and 36.8% in the control group.

The most common adverse events in both groups included nausea, diarrhea, vomiting, fatigue, appetite loss, and alopecia. About 10% of patients in the targeted therapy group and 9% of those in the control group discontinued their treatment early, suggesting the severity of side effects was similar between the groups.

Kopetz cautioned that the data are still early and follow-up is ongoing. However, he said, the findings support the targeted drugs plus FOLFIRI as a “potential new standard of care” for this patient population.

“The addition of FOLFIRI chemotherapy in the frontline setting will give oncologists and patients more options when selecting a first-line regimen,” Saltzman said. “To have as many options as possible is certainly something we all hope for.”

The trial was funded by Pfizer. Kopetz reported consulting for Pfizer and several other pharmaceutical companies. Saltzman reported having no disclosures.

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

TOPLINE:

A randomized trial of 32 patients with advanced pancreatic cancer found that early access to medical cannabis patients' symptom burden, with minimal side effects.

METHODOLOGY:

• Patients with pancreatic cancer commonly experience moderate-to-severe pain, nausea, insomnia, and other symptoms that significantly affect their quality of life. Current management approaches are insufficient. Preliminary evidence suggests that medical cannabis has efficacy against multiple cancer-related symptoms, but high-quality data remain limited due to regulatory barriers.
• Researchers conducted a pilot randomized, waitlist-controlled trial involving 32 patients (median age, 71 years) with newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma and at least one burdensome symptom.
• Patients were randomly assigned in a 1:1 ratio to early (0-8 weeks) or delayed (9-16 weeks) cannabis intervention through the Minnesota Medical Cannabis Program, which provided cannabis products and education in how to use them.
• Primary outcomes focused on feasibility, while secondary outcomes examined acceptability, changes in symptom burden, and quality of life in exploratory efficacy analyses.

TAKEAWAY:

• At baseline, patients reported a substantial moderate-to-severe symptom burden — most commonly insomnia (85%), pain (77%), and appetite loss (69%); 10 patients (31%) were using opioids.
• The study met all of its feasibility metrics, with 74% of the patients meeting enrollment eligibility and 81% complying with their random assignment. Patients in the arm with early cannabis access typically picked up their products 3 days after starting chemotherapy. Most used tablets or other oral cannabis formulations.
• At 8 weeks, patients in the early-access arm experienced numerically higher rates of improvement in pain (44% vs 20%; P = .35), appetite (56% vs 30%; P = .37), and insomnia (67% vs 30%; P = .18), as well as a reduction in opioid use. Their rates of potential cannabis side effects, including dry mouth, dizziness, and concentration problems, were lower compared with the waitlist group — possibly, the authors noted, due to their education to “start low, go slow.”
• Patients made a median of two trips to a cannabis dispensary during the study period, and most said that using cannabis was “easy” and “practical.”

IN PRACTICE:

“Early access to medical cannabis was associated with improvement in certain symptoms, such as insomnia, with minimal harms,” the authors wrote, adding that the research design offers a model collaboration between investigators and state cannabis programs.

“The encouraging preliminary efficacy and safety of cannabis in managing symptoms supports further exploration," they concluded.

SOURCE:

The study was led by Dylan Zylla, MD, MS, of HealthPartners Institute, Cancer Research Center, Minneapolis, Minnesota. It was presented on January 9 at the ASCO Gastrointestinal Cancers Symposium 2026 and simultaneously published in JCO Oncology Practice.

LIMITATIONS:

The trial was small and the 8-week primary study period precluded conclusions about longer-term benefits and safety. Generalizability may be limited as the trial was conducted in a single state with a predominantly urban and White patient population. Additionally, heterogeneity in state cannabis programs and laws may limit national applicability.

DISCLOSURES:

The study was supported by philanthropic support to the HealthPartners Cancer Research Center. Cannabis products were provided by Vireo Health (GreenGoods, Minnesota). Additional disclosures are noted in the original article.

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:

A randomized trial of 32 patients with advanced pancreatic cancer found that early access to medical cannabis patients' symptom burden, with minimal side effects.

METHODOLOGY:

• Patients with pancreatic cancer commonly experience moderate-to-severe pain, nausea, insomnia, and other symptoms that significantly affect their quality of life. Current management approaches are insufficient. Preliminary evidence suggests that medical cannabis has efficacy against multiple cancer-related symptoms, but high-quality data remain limited due to regulatory barriers.
• Researchers conducted a pilot randomized, waitlist-controlled trial involving 32 patients (median age, 71 years) with newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma and at least one burdensome symptom.
• Patients were randomly assigned in a 1:1 ratio to early (0-8 weeks) or delayed (9-16 weeks) cannabis intervention through the Minnesota Medical Cannabis Program, which provided cannabis products and education in how to use them.
• Primary outcomes focused on feasibility, while secondary outcomes examined acceptability, changes in symptom burden, and quality of life in exploratory efficacy analyses.

TAKEAWAY:

• At baseline, patients reported a substantial moderate-to-severe symptom burden — most commonly insomnia (85%), pain (77%), and appetite loss (69%); 10 patients (31%) were using opioids.
• The study met all of its feasibility metrics, with 74% of the patients meeting enrollment eligibility and 81% complying with their random assignment. Patients in the arm with early cannabis access typically picked up their products 3 days after starting chemotherapy. Most used tablets or other oral cannabis formulations.
• At 8 weeks, patients in the early-access arm experienced numerically higher rates of improvement in pain (44% vs 20%; P = .35), appetite (56% vs 30%; P = .37), and insomnia (67% vs 30%; P = .18), as well as a reduction in opioid use. Their rates of potential cannabis side effects, including dry mouth, dizziness, and concentration problems, were lower compared with the waitlist group — possibly, the authors noted, due to their education to “start low, go slow.”
• Patients made a median of two trips to a cannabis dispensary during the study period, and most said that using cannabis was “easy” and “practical.”

IN PRACTICE:

“Early access to medical cannabis was associated with improvement in certain symptoms, such as insomnia, with minimal harms,” the authors wrote, adding that the research design offers a model collaboration between investigators and state cannabis programs.

“The encouraging preliminary efficacy and safety of cannabis in managing symptoms supports further exploration," they concluded.

SOURCE:

The study was led by Dylan Zylla, MD, MS, of HealthPartners Institute, Cancer Research Center, Minneapolis, Minnesota. It was presented on January 9 at the ASCO Gastrointestinal Cancers Symposium 2026 and simultaneously published in JCO Oncology Practice.

LIMITATIONS:

The trial was small and the 8-week primary study period precluded conclusions about longer-term benefits and safety. Generalizability may be limited as the trial was conducted in a single state with a predominantly urban and White patient population. Additionally, heterogeneity in state cannabis programs and laws may limit national applicability.

DISCLOSURES:

The study was supported by philanthropic support to the HealthPartners Cancer Research Center. Cannabis products were provided by Vireo Health (GreenGoods, Minnesota). Additional disclosures are noted in the original article.

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:

A randomized trial of 32 patients with advanced pancreatic cancer found that early access to medical cannabis patients' symptom burden, with minimal side effects.

METHODOLOGY:

• Patients with pancreatic cancer commonly experience moderate-to-severe pain, nausea, insomnia, and other symptoms that significantly affect their quality of life. Current management approaches are insufficient. Preliminary evidence suggests that medical cannabis has efficacy against multiple cancer-related symptoms, but high-quality data remain limited due to regulatory barriers.
• Researchers conducted a pilot randomized, waitlist-controlled trial involving 32 patients (median age, 71 years) with newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma and at least one burdensome symptom.
• Patients were randomly assigned in a 1:1 ratio to early (0-8 weeks) or delayed (9-16 weeks) cannabis intervention through the Minnesota Medical Cannabis Program, which provided cannabis products and education in how to use them.
• Primary outcomes focused on feasibility, while secondary outcomes examined acceptability, changes in symptom burden, and quality of life in exploratory efficacy analyses.

TAKEAWAY:

• At baseline, patients reported a substantial moderate-to-severe symptom burden — most commonly insomnia (85%), pain (77%), and appetite loss (69%); 10 patients (31%) were using opioids.
• The study met all of its feasibility metrics, with 74% of the patients meeting enrollment eligibility and 81% complying with their random assignment. Patients in the arm with early cannabis access typically picked up their products 3 days after starting chemotherapy. Most used tablets or other oral cannabis formulations.
• At 8 weeks, patients in the early-access arm experienced numerically higher rates of improvement in pain (44% vs 20%; P = .35), appetite (56% vs 30%; P = .37), and insomnia (67% vs 30%; P = .18), as well as a reduction in opioid use. Their rates of potential cannabis side effects, including dry mouth, dizziness, and concentration problems, were lower compared with the waitlist group — possibly, the authors noted, due to their education to “start low, go slow.”
• Patients made a median of two trips to a cannabis dispensary during the study period, and most said that using cannabis was “easy” and “practical.”

IN PRACTICE:

“Early access to medical cannabis was associated with improvement in certain symptoms, such as insomnia, with minimal harms,” the authors wrote, adding that the research design offers a model collaboration between investigators and state cannabis programs.

“The encouraging preliminary efficacy and safety of cannabis in managing symptoms supports further exploration," they concluded.

SOURCE:

The study was led by Dylan Zylla, MD, MS, of HealthPartners Institute, Cancer Research Center, Minneapolis, Minnesota. It was presented on January 9 at the ASCO Gastrointestinal Cancers Symposium 2026 and simultaneously published in JCO Oncology Practice.

LIMITATIONS:

The trial was small and the 8-week primary study period precluded conclusions about longer-term benefits and safety. Generalizability may be limited as the trial was conducted in a single state with a predominantly urban and White patient population. Additionally, heterogeneity in state cannabis programs and laws may limit national applicability.

DISCLOSURES:

The study was supported by philanthropic support to the HealthPartners Cancer Research Center. Cannabis products were provided by Vireo Health (GreenGoods, Minnesota). Additional disclosures are noted in the original article.

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:

A recent analysis suggested that home-based screening for anal cancer is a cost-effective way to increase screening compared to clinic-based screening. The study found that a home-based approach led to higher participation rates (89.2% vs 74.2% for a clinic-based approach) among sexual and gender minority individuals and was cost-effective, costing $25.19 per additional individual screened when accounting for both direct and indirect costs and $132.36 per additional individual screened when only accounting for direct medical costs.

METHODOLOGY:

• Anal cancer screening is recommended for high-risk populations, such as sexual and gender minority individuals. However, it's unclear how cost-effective home-based self-sampling is compared to clinic-based screening.
• Researchers conducted an economic evaluation using data from a randomized clinical trial that included 240 sexual and gender minority individuals in Milwaukee from January 2020 to August 2022.
• Participants, aged ≥ 25 years, were randomized to either home-based self-sampling or clinic-based screening.
• Researchers evaluated direct home-based screening costs from the trial, and sourced clinic-based costs from the Medicare reimbursement schedule. Travel and time costs were determined from participant self-reports.
• The primary outcome was the incremental cost-effectiveness ratio (ICER), which was the additional cost needed to increase screening participation by one person. The researchers calculated ICERs from both a healthcare payer and societal perspective. The healthcare perspective included only direct medical costs and the societal perspective accounted for direct medical costs as well as indirect time and travel costs.

TAKEAWAY:

• Home-based screening led to higher participation rates than clinic-based screening—89.2% vs 74.2%—with 107 participants completing home-based screening compared with 89 participants doing clinic-based screening.
• The cost per participant was $64.18 for home-based screening and $60.40 for clinic-based screening from the societal perspective, and $61.91 for home-based screening and $42.06 for clinic-based screening from the healthcare payer perspective.
• With home-based screening, the ICER per additional screened participant was $25.19 from a societal perspective and $132.36 from a healthcare payer perspective.
• From the societal perspective, the probability that home-based screening was cost-effective compared with clinic-based screening was nearly 50% at a willingness-to-pay threshold of $25 and 99.99% at a threshold of $100. From the healthcare perspective, the probability was 3.8% at a threshold of $100 and 90.9% at a threshold of $200.

IN PRACTICE:

"These findings suggest that home-based screening promises to be a cost-effective option to enhance anal cancer screening participation," the study authors concluded.

SOURCE:

The study, led by Haluk Damgacioglu, PhD, Department of Public Health Sciences, Medical University of South Carolina in Charleston, South Carolina, was published online in JAMA Network Open.

LIMITATIONS:

The study was conducted in an urban setting where proximity to clinics may reduce structural barriers, potentially limiting generalizability to rural areas where longer travel distances and limited clinician availability could affect participation rates. The analysis did not include downstream steps such as follow-up clinic visits, confirmatory testing, treatment of precancerous lesions, or cancer prevention outcomes. While home-based screening participants were required to visit clinics for digital anal rectal examination to exclude prevalent anal cancer, these follow-up visit costs were not included in the cost-effectiveness analysis.

DISCLOSURES:

Elizabeth Chiao, PhD, reported receiving grants from the National Institutes of Health during the study. Jennifer S. Smith, PhD, MPH, disclosed receiving personal fees from Hologic, Inc., and materials for research purposes from Rovers Medical Devices. Ashish A. Deshmukh, PhD, MPH, reported receiving personal fees from Value Analytics Lab. Alan G. Nyitray, PhD, reported receiving grants from the National Cancer Institute and test kits from Copan Diagnostics.

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:

A recent analysis suggested that home-based screening for anal cancer is a cost-effective way to increase screening compared to clinic-based screening. The study found that a home-based approach led to higher participation rates (89.2% vs 74.2% for a clinic-based approach) among sexual and gender minority individuals and was cost-effective, costing $25.19 per additional individual screened when accounting for both direct and indirect costs and $132.36 per additional individual screened when only accounting for direct medical costs.

METHODOLOGY:

• Anal cancer screening is recommended for high-risk populations, such as sexual and gender minority individuals. However, it's unclear how cost-effective home-based self-sampling is compared to clinic-based screening.
• Researchers conducted an economic evaluation using data from a randomized clinical trial that included 240 sexual and gender minority individuals in Milwaukee from January 2020 to August 2022.
• Participants, aged ≥ 25 years, were randomized to either home-based self-sampling or clinic-based screening.
• Researchers evaluated direct home-based screening costs from the trial, and sourced clinic-based costs from the Medicare reimbursement schedule. Travel and time costs were determined from participant self-reports.
• The primary outcome was the incremental cost-effectiveness ratio (ICER), which was the additional cost needed to increase screening participation by one person. The researchers calculated ICERs from both a healthcare payer and societal perspective. The healthcare perspective included only direct medical costs and the societal perspective accounted for direct medical costs as well as indirect time and travel costs.

TAKEAWAY:

• Home-based screening led to higher participation rates than clinic-based screening—89.2% vs 74.2%—with 107 participants completing home-based screening compared with 89 participants doing clinic-based screening.
• The cost per participant was $64.18 for home-based screening and $60.40 for clinic-based screening from the societal perspective, and $61.91 for home-based screening and $42.06 for clinic-based screening from the healthcare payer perspective.
• With home-based screening, the ICER per additional screened participant was $25.19 from a societal perspective and $132.36 from a healthcare payer perspective.
• From the societal perspective, the probability that home-based screening was cost-effective compared with clinic-based screening was nearly 50% at a willingness-to-pay threshold of $25 and 99.99% at a threshold of $100. From the healthcare perspective, the probability was 3.8% at a threshold of $100 and 90.9% at a threshold of $200.

IN PRACTICE:

"These findings suggest that home-based screening promises to be a cost-effective option to enhance anal cancer screening participation," the study authors concluded.

SOURCE:

The study, led by Haluk Damgacioglu, PhD, Department of Public Health Sciences, Medical University of South Carolina in Charleston, South Carolina, was published online in JAMA Network Open.

LIMITATIONS:

The study was conducted in an urban setting where proximity to clinics may reduce structural barriers, potentially limiting generalizability to rural areas where longer travel distances and limited clinician availability could affect participation rates. The analysis did not include downstream steps such as follow-up clinic visits, confirmatory testing, treatment of precancerous lesions, or cancer prevention outcomes. While home-based screening participants were required to visit clinics for digital anal rectal examination to exclude prevalent anal cancer, these follow-up visit costs were not included in the cost-effectiveness analysis.

DISCLOSURES:

Elizabeth Chiao, PhD, reported receiving grants from the National Institutes of Health during the study. Jennifer S. Smith, PhD, MPH, disclosed receiving personal fees from Hologic, Inc., and materials for research purposes from Rovers Medical Devices. Ashish A. Deshmukh, PhD, MPH, reported receiving personal fees from Value Analytics Lab. Alan G. Nyitray, PhD, reported receiving grants from the National Cancer Institute and test kits from Copan Diagnostics.

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:

A recent analysis suggested that home-based screening for anal cancer is a cost-effective way to increase screening compared to clinic-based screening. The study found that a home-based approach led to higher participation rates (89.2% vs 74.2% for a clinic-based approach) among sexual and gender minority individuals and was cost-effective, costing $25.19 per additional individual screened when accounting for both direct and indirect costs and $132.36 per additional individual screened when only accounting for direct medical costs.

METHODOLOGY:

• Anal cancer screening is recommended for high-risk populations, such as sexual and gender minority individuals. However, it's unclear how cost-effective home-based self-sampling is compared to clinic-based screening.
• Researchers conducted an economic evaluation using data from a randomized clinical trial that included 240 sexual and gender minority individuals in Milwaukee from January 2020 to August 2022.
• Participants, aged ≥ 25 years, were randomized to either home-based self-sampling or clinic-based screening.
• Researchers evaluated direct home-based screening costs from the trial, and sourced clinic-based costs from the Medicare reimbursement schedule. Travel and time costs were determined from participant self-reports.
• The primary outcome was the incremental cost-effectiveness ratio (ICER), which was the additional cost needed to increase screening participation by one person. The researchers calculated ICERs from both a healthcare payer and societal perspective. The healthcare perspective included only direct medical costs and the societal perspective accounted for direct medical costs as well as indirect time and travel costs.

TAKEAWAY:

• Home-based screening led to higher participation rates than clinic-based screening—89.2% vs 74.2%—with 107 participants completing home-based screening compared with 89 participants doing clinic-based screening.
• The cost per participant was $64.18 for home-based screening and $60.40 for clinic-based screening from the societal perspective, and $61.91 for home-based screening and $42.06 for clinic-based screening from the healthcare payer perspective.
• With home-based screening, the ICER per additional screened participant was $25.19 from a societal perspective and $132.36 from a healthcare payer perspective.
• From the societal perspective, the probability that home-based screening was cost-effective compared with clinic-based screening was nearly 50% at a willingness-to-pay threshold of $25 and 99.99% at a threshold of $100. From the healthcare perspective, the probability was 3.8% at a threshold of $100 and 90.9% at a threshold of $200.

IN PRACTICE:

"These findings suggest that home-based screening promises to be a cost-effective option to enhance anal cancer screening participation," the study authors concluded.

SOURCE:

The study, led by Haluk Damgacioglu, PhD, Department of Public Health Sciences, Medical University of South Carolina in Charleston, South Carolina, was published online in JAMA Network Open.

LIMITATIONS:

The study was conducted in an urban setting where proximity to clinics may reduce structural barriers, potentially limiting generalizability to rural areas where longer travel distances and limited clinician availability could affect participation rates. The analysis did not include downstream steps such as follow-up clinic visits, confirmatory testing, treatment of precancerous lesions, or cancer prevention outcomes. While home-based screening participants were required to visit clinics for digital anal rectal examination to exclude prevalent anal cancer, these follow-up visit costs were not included in the cost-effectiveness analysis.

DISCLOSURES:

Elizabeth Chiao, PhD, reported receiving grants from the National Institutes of Health during the study. Jennifer S. Smith, PhD, MPH, disclosed receiving personal fees from Hologic, Inc., and materials for research purposes from Rovers Medical Devices. Ashish A. Deshmukh, PhD, MPH, reported receiving personal fees from Value Analytics Lab. Alan G. Nyitray, PhD, reported receiving grants from the National Cancer Institute and test kits from Copan Diagnostics.

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:

Rural cancer survivors experience significantly higher rates of chronic pain at 43.0% than those among urban survivors at 33.5%. Even after controlling for demographics and health conditions, rural residents showed 21% higher odds of experiencing chronic pain.

METHODOLOGY:

• Chronic pain prevalence among cancer survivors is twice that of the general US population and is associated with numerous negative outcomes. Rural residence is frequently linked to debilitating long-term survivorship effects, and current data lack information on whether chronic pain disparity exists specifically for rural cancer survivors.
• Researchers pooled data from the 2019–2021 and 2023 National Health Interview Survey, a cross–sectional survey conducted by the National Center for Health Statistics.
• Analysis included 5542 adult cancer survivors diagnosed within the previous 5 years, with 51.6% female participants and 48.4% male participants.
• Chronic pain was defined as pain experienced on most or all days over the past 3 months, following National Center for Health Statistics conventions.
• Rural residence classification was based on noncore or nonmetropolitan counties using the modified National Center for Health Statistics Urban–Rural Classification Scheme for Counties.

TAKEAWAY:

• Rural cancer survivors showed significantly higher odds of experiencing chronic pain compared with urban survivors (odds ratio [OR], 1.21; 95% CI, 1.01-1.45).
• Rural survivors were more likely to be non–Hispanic White, have less than a 4-year college degree, have an income below 200% of the federal poverty level, and have slightly more chronic health conditions.
• Having an income below 100% of the federal poverty level was associated with doubled odds of chronic pain (OR, 2.07; 95% CI, 1.54-2.77) compared with having an income at least four times the federal poverty level.
• Each additional health condition increased the odds of experiencing chronic pain by 32% (OR, 1.32; 95% CI, 1.26-1.39).

IN PRACTICE:

“Policymakers and health systems should work to close this gap by increasing the availability of pain management resources for rural cancer survivors. Approaches could include innovative payment models for integrative medicine in rural areas or supporting rural clinician access to pain specialists,” the authors of the study wrote.

SOURCE:

This study was led by Hyojin Choi, PhD, Department of Family Medicine, The Robert Larner MD College of Medicine, University of Vermont in Burlington, Vermont. It was published online in JAMA Network Open.

LIMITATIONS:

The authors note that the cross–sectional design of the study and limited information on individual respondents’ use of multimodal pain treatment options constrain the interpretation of findings.

DISCLOSURES:

The authors did not report any relevant conflicts of interest.

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:

Rural cancer survivors experience significantly higher rates of chronic pain at 43.0% than those among urban survivors at 33.5%. Even after controlling for demographics and health conditions, rural residents showed 21% higher odds of experiencing chronic pain.

METHODOLOGY:

• Chronic pain prevalence among cancer survivors is twice that of the general US population and is associated with numerous negative outcomes. Rural residence is frequently linked to debilitating long-term survivorship effects, and current data lack information on whether chronic pain disparity exists specifically for rural cancer survivors.
• Researchers pooled data from the 2019–2021 and 2023 National Health Interview Survey, a cross–sectional survey conducted by the National Center for Health Statistics.
• Analysis included 5542 adult cancer survivors diagnosed within the previous 5 years, with 51.6% female participants and 48.4% male participants.
• Chronic pain was defined as pain experienced on most or all days over the past 3 months, following National Center for Health Statistics conventions.
• Rural residence classification was based on noncore or nonmetropolitan counties using the modified National Center for Health Statistics Urban–Rural Classification Scheme for Counties.

TAKEAWAY:

• Rural cancer survivors showed significantly higher odds of experiencing chronic pain compared with urban survivors (odds ratio [OR], 1.21; 95% CI, 1.01-1.45).
• Rural survivors were more likely to be non–Hispanic White, have less than a 4-year college degree, have an income below 200% of the federal poverty level, and have slightly more chronic health conditions.
• Having an income below 100% of the federal poverty level was associated with doubled odds of chronic pain (OR, 2.07; 95% CI, 1.54-2.77) compared with having an income at least four times the federal poverty level.
• Each additional health condition increased the odds of experiencing chronic pain by 32% (OR, 1.32; 95% CI, 1.26-1.39).

IN PRACTICE:

“Policymakers and health systems should work to close this gap by increasing the availability of pain management resources for rural cancer survivors. Approaches could include innovative payment models for integrative medicine in rural areas or supporting rural clinician access to pain specialists,” the authors of the study wrote.

SOURCE:

This study was led by Hyojin Choi, PhD, Department of Family Medicine, The Robert Larner MD College of Medicine, University of Vermont in Burlington, Vermont. It was published online in JAMA Network Open.

LIMITATIONS:

The authors note that the cross–sectional design of the study and limited information on individual respondents’ use of multimodal pain treatment options constrain the interpretation of findings.

DISCLOSURES:

The authors did not report any relevant conflicts of interest.

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:

Rural cancer survivors experience significantly higher rates of chronic pain at 43.0% than those among urban survivors at 33.5%. Even after controlling for demographics and health conditions, rural residents showed 21% higher odds of experiencing chronic pain.

METHODOLOGY:

• Chronic pain prevalence among cancer survivors is twice that of the general US population and is associated with numerous negative outcomes. Rural residence is frequently linked to debilitating long-term survivorship effects, and current data lack information on whether chronic pain disparity exists specifically for rural cancer survivors.
• Researchers pooled data from the 2019–2021 and 2023 National Health Interview Survey, a cross–sectional survey conducted by the National Center for Health Statistics.
• Analysis included 5542 adult cancer survivors diagnosed within the previous 5 years, with 51.6% female participants and 48.4% male participants.
• Chronic pain was defined as pain experienced on most or all days over the past 3 months, following National Center for Health Statistics conventions.
• Rural residence classification was based on noncore or nonmetropolitan counties using the modified National Center for Health Statistics Urban–Rural Classification Scheme for Counties.

TAKEAWAY:

• Rural cancer survivors showed significantly higher odds of experiencing chronic pain compared with urban survivors (odds ratio [OR], 1.21; 95% CI, 1.01-1.45).
• Rural survivors were more likely to be non–Hispanic White, have less than a 4-year college degree, have an income below 200% of the federal poverty level, and have slightly more chronic health conditions.
• Having an income below 100% of the federal poverty level was associated with doubled odds of chronic pain (OR, 2.07; 95% CI, 1.54-2.77) compared with having an income at least four times the federal poverty level.
• Each additional health condition increased the odds of experiencing chronic pain by 32% (OR, 1.32; 95% CI, 1.26-1.39).

IN PRACTICE:

“Policymakers and health systems should work to close this gap by increasing the availability of pain management resources for rural cancer survivors. Approaches could include innovative payment models for integrative medicine in rural areas or supporting rural clinician access to pain specialists,” the authors of the study wrote.

SOURCE:

This study was led by Hyojin Choi, PhD, Department of Family Medicine, The Robert Larner MD College of Medicine, University of Vermont in Burlington, Vermont. It was published online in JAMA Network Open.

LIMITATIONS:

The authors note that the cross–sectional design of the study and limited information on individual respondents’ use of multimodal pain treatment options constrain the interpretation of findings.

DISCLOSURES:

The authors did not report any relevant conflicts of interest.

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.

Adding teclistamab to daratumumab dramatically improved progression-free survival and overall survival vs standard-of-care (SOC) therapy in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 MajesTEC-3 trial.

At median follow-up of 34.5 months, progression-free survival was not reached in study participants randomized to receive teclistamab plus daratumumab (Tec-Dara). Starkly contrasting that was the 18.1 months progression-free survival among those randomized to a control group who received the standard of care: investigator’s choice of daratumumab and dexamethasone plus either pomalidomide or bortezomib (DPd/DVd (hazard ratio [HR], 0.17). Overall survival also significantly favored Tec-Dara (HR, 0.46).

Lead investigator María-Victoria Mateos, MD, PhD, reported the findings in a late-breaking abstract session at American Society of Hematology (ASH) 2025 Annual Meeting. They were published simultaneously in The New England Journal of Medicine.

“[Tec-Dara in this setting] generated the greatest progression-free survival treatment effect to date [in RRMR] with a plateau phase after 6 months of therapy, suggesting potential for functional cure,” said Mateos, a consultant physician and associate professor at the University of Salamanca, Salamanca, Spain.

“We consider that this synergistic immunotherapy combination…is a new potential standard of care for relapsed or refractory multiple myeloma after at least on prior line of therapy, with broad potential across academic and community settings,” added Mateos, who also directs the Multiple Myeloma Program at the University.

Based on the MajesTEC-3 findings, the FDA proactively awarded a national priority voucher to Tec-Dara under the Commissioner’s National Priority Voucher pilot program designed to accelerate the review of certain promising products.

About Tec-Dara

Teclistamab (Tecvayli) is an off-the-shelf first-in-class bispecific monoclonal antibody shown in the MajesTEC-1 trial to provide deep, durable responses in RRMM, with improved efficacy and safety with earlier lines of therapy. The FDA approved the agent for use in 4th or greater lines of therapy in 2022 based on those findings.

Daratumumab (Darzalex) is a widely used anti-CD38 monoclonal antibody currently considered the SOC therapy for RRMM. Both agents are products of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Although front-line therapy for multiple myeloma has dramatically improved, there is a need for new, more effective treatment strategies in patients with disease progression, Mateos noted.

Therefore, she and her colleagues conducted MajesTEC-3, a randomized trial exploring the fully immunotherapy-based regimen of Tec-Dara vs daratumumab-based SOC in patients who had received one to three prior lines of therapy, including a proteasome inhibitor and lenalidomide (Len).

The study was the first to test a bispecific monoclonal antibody as early as the first relapse after initial treatment, she noted.

About MajesTEC-3

Study participants were 587 adults aged 25-88 years. Those with one prior line of therapy were required to be Len-refractory with progressive disease on or after the last therapy. Prior anti-CD-38 Patients with prior B-cell maturation antigen-directed therapy or who were refractory to anti-CD38 treatment were excluded.

The 291 patients randomized to the Tec-Dara treatment group and 296 randomized to the control group were treated in 28-day cycles according to the standard daratumumab schedule: weekly treatment during cycles 1 and 2, biweekly treatment during cycles 3-6, and monthly treatments beginning with cycle 7.

Teclistamab was initiated with an approved step-up dose school followed by 1.5 mg/kg weekly in cycles 1 and 2, 3 mg/kg biweekly in cycles 3-6, and 3 mg/kg monthly beginning with cycle 7.

The 36-month progression-free survival rates with Tec-Dara vs DPd/DVd were 83.4% and 29.7%, with the 36-month overall survival rates having been 83.3% and 65.0%. More than 90% of patients in the Tec-Dara group who were alive at 6 months were also alive at 30 months, Mateos noted.

For both progression-free survival and overall survival, the “clinically remarkable and statistically significant” differences were apparent across all prespecified and clinically relevant subgroups, she added. These included patients who were 75 years or older, Len-refractory patients, and those with high-risk cytogenetics, ≥ 60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposure.

Patients receiving Tec-Dara also had significantly higher rates of complete or better responses (81.8% vs 32.1%; odds ratio [OR], 9.56), overall response (89.0% vs 75.3%; OR, 2.65), and minimal residual disease-negativity (58.4% vs 17.1%; OR, 6.78).

The median time to first response and first complete or better response was similar in the two groups, but 36-month duration of response was 88.5 vs 36.4 months. At data cutoff, 49.4% of patients remained on study treatment — 71.0% in the Tec-Dara group and 28.3% in the DPd/DVd group, and median treatment duration was twice as long with Tec-Dara (32.4 vs 16.1 months), she said.

Serious adverse events occurred at similar rates in the treatment and control groups (70.7% and 62.4%) and most (44.2%) were grade 1 cytokine release syndrome (CRS). No grade 3 CRS occurred, and all CRS cases resolved.

Immune effector-cell-associated neurotoxicity occurred in 1.1% of patients, and all cases resolved.

Treatment-related adverse events leading to discontinuation occurred in 4.6% and 5.5% of patients in the Tec-Dara and DPd/DVd groups. The rates of deaths due to treatment-emergent adverse events were also similar in the groups (7.1% vs 5.9%).

Infections of any grade occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd patients, and grade 3/4 infections occurred in 54.1% and 43.4%. New-onset grade 3 or greater infections decreased over time.

“It’s important to acknowledge that patients with infections needed to be supported with adequate prophylaxis and immunoglobulins,” Mateo stressed.

Implications for Patients With RRMM

Teclistamab is currently only approved after three prior lines of therapy, but under the FDA Commissioner’s National Priority Voucher program, the agency will aim to complete its review of Tec-Dara for earlier treatment within 1-2 months following submission of an application for approval by Johnson & Johnson.

If an approval for that indication were to occur, it would be transformative for patients with RRMM, said Michael Rosenzweig, MD, of City of Hope, Duarte, California, in an interview with Medscape Medical News.

The [MajesTEC-3] findings suggest that Tec-Dar “really gives patients a chance at long-term disease control,” added Rosenzweig, chief of the Division of Multiple Myeloma, and an associate professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

MajesTEC-3 was funded by Johnson & Johnson. Mateos disclosed relationships with numerous pharmaceutical companies, including Johnson & Johnson. Rosenzweig reported consulting for Johnson & Johnson and was previously on the company’s speakers bureau.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and health care topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.

Adding teclistamab to daratumumab dramatically improved progression-free survival and overall survival vs standard-of-care (SOC) therapy in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 MajesTEC-3 trial.

At median follow-up of 34.5 months, progression-free survival was not reached in study participants randomized to receive teclistamab plus daratumumab (Tec-Dara). Starkly contrasting that was the 18.1 months progression-free survival among those randomized to a control group who received the standard of care: investigator’s choice of daratumumab and dexamethasone plus either pomalidomide or bortezomib (DPd/DVd (hazard ratio [HR], 0.17). Overall survival also significantly favored Tec-Dara (HR, 0.46).

Lead investigator María-Victoria Mateos, MD, PhD, reported the findings in a late-breaking abstract session at American Society of Hematology (ASH) 2025 Annual Meeting. They were published simultaneously in The New England Journal of Medicine.

“[Tec-Dara in this setting] generated the greatest progression-free survival treatment effect to date [in RRMR] with a plateau phase after 6 months of therapy, suggesting potential for functional cure,” said Mateos, a consultant physician and associate professor at the University of Salamanca, Salamanca, Spain.

“We consider that this synergistic immunotherapy combination…is a new potential standard of care for relapsed or refractory multiple myeloma after at least on prior line of therapy, with broad potential across academic and community settings,” added Mateos, who also directs the Multiple Myeloma Program at the University.

Based on the MajesTEC-3 findings, the FDA proactively awarded a national priority voucher to Tec-Dara under the Commissioner’s National Priority Voucher pilot program designed to accelerate the review of certain promising products.

About Tec-Dara

Teclistamab (Tecvayli) is an off-the-shelf first-in-class bispecific monoclonal antibody shown in the MajesTEC-1 trial to provide deep, durable responses in RRMM, with improved efficacy and safety with earlier lines of therapy. The FDA approved the agent for use in 4th or greater lines of therapy in 2022 based on those findings.

Daratumumab (Darzalex) is a widely used anti-CD38 monoclonal antibody currently considered the SOC therapy for RRMM. Both agents are products of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Although front-line therapy for multiple myeloma has dramatically improved, there is a need for new, more effective treatment strategies in patients with disease progression, Mateos noted.

Therefore, she and her colleagues conducted MajesTEC-3, a randomized trial exploring the fully immunotherapy-based regimen of Tec-Dara vs daratumumab-based SOC in patients who had received one to three prior lines of therapy, including a proteasome inhibitor and lenalidomide (Len).

The study was the first to test a bispecific monoclonal antibody as early as the first relapse after initial treatment, she noted.

About MajesTEC-3

Study participants were 587 adults aged 25-88 years. Those with one prior line of therapy were required to be Len-refractory with progressive disease on or after the last therapy. Prior anti-CD-38 Patients with prior B-cell maturation antigen-directed therapy or who were refractory to anti-CD38 treatment were excluded.

The 291 patients randomized to the Tec-Dara treatment group and 296 randomized to the control group were treated in 28-day cycles according to the standard daratumumab schedule: weekly treatment during cycles 1 and 2, biweekly treatment during cycles 3-6, and monthly treatments beginning with cycle 7.

Teclistamab was initiated with an approved step-up dose school followed by 1.5 mg/kg weekly in cycles 1 and 2, 3 mg/kg biweekly in cycles 3-6, and 3 mg/kg monthly beginning with cycle 7.

The 36-month progression-free survival rates with Tec-Dara vs DPd/DVd were 83.4% and 29.7%, with the 36-month overall survival rates having been 83.3% and 65.0%. More than 90% of patients in the Tec-Dara group who were alive at 6 months were also alive at 30 months, Mateos noted.

For both progression-free survival and overall survival, the “clinically remarkable and statistically significant” differences were apparent across all prespecified and clinically relevant subgroups, she added. These included patients who were 75 years or older, Len-refractory patients, and those with high-risk cytogenetics, ≥ 60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposure.

Patients receiving Tec-Dara also had significantly higher rates of complete or better responses (81.8% vs 32.1%; odds ratio [OR], 9.56), overall response (89.0% vs 75.3%; OR, 2.65), and minimal residual disease-negativity (58.4% vs 17.1%; OR, 6.78).

The median time to first response and first complete or better response was similar in the two groups, but 36-month duration of response was 88.5 vs 36.4 months. At data cutoff, 49.4% of patients remained on study treatment — 71.0% in the Tec-Dara group and 28.3% in the DPd/DVd group, and median treatment duration was twice as long with Tec-Dara (32.4 vs 16.1 months), she said.

Serious adverse events occurred at similar rates in the treatment and control groups (70.7% and 62.4%) and most (44.2%) were grade 1 cytokine release syndrome (CRS). No grade 3 CRS occurred, and all CRS cases resolved.

Immune effector-cell-associated neurotoxicity occurred in 1.1% of patients, and all cases resolved.

Treatment-related adverse events leading to discontinuation occurred in 4.6% and 5.5% of patients in the Tec-Dara and DPd/DVd groups. The rates of deaths due to treatment-emergent adverse events were also similar in the groups (7.1% vs 5.9%).

Infections of any grade occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd patients, and grade 3/4 infections occurred in 54.1% and 43.4%. New-onset grade 3 or greater infections decreased over time.

“It’s important to acknowledge that patients with infections needed to be supported with adequate prophylaxis and immunoglobulins,” Mateo stressed.

Implications for Patients With RRMM

Teclistamab is currently only approved after three prior lines of therapy, but under the FDA Commissioner’s National Priority Voucher program, the agency will aim to complete its review of Tec-Dara for earlier treatment within 1-2 months following submission of an application for approval by Johnson & Johnson.

If an approval for that indication were to occur, it would be transformative for patients with RRMM, said Michael Rosenzweig, MD, of City of Hope, Duarte, California, in an interview with Medscape Medical News.

The [MajesTEC-3] findings suggest that Tec-Dar “really gives patients a chance at long-term disease control,” added Rosenzweig, chief of the Division of Multiple Myeloma, and an associate professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

MajesTEC-3 was funded by Johnson & Johnson. Mateos disclosed relationships with numerous pharmaceutical companies, including Johnson & Johnson. Rosenzweig reported consulting for Johnson & Johnson and was previously on the company’s speakers bureau.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and health care topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.

Adding teclistamab to daratumumab dramatically improved progression-free survival and overall survival vs standard-of-care (SOC) therapy in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 MajesTEC-3 trial.

At median follow-up of 34.5 months, progression-free survival was not reached in study participants randomized to receive teclistamab plus daratumumab (Tec-Dara). Starkly contrasting that was the 18.1 months progression-free survival among those randomized to a control group who received the standard of care: investigator’s choice of daratumumab and dexamethasone plus either pomalidomide or bortezomib (DPd/DVd (hazard ratio [HR], 0.17). Overall survival also significantly favored Tec-Dara (HR, 0.46).

Lead investigator María-Victoria Mateos, MD, PhD, reported the findings in a late-breaking abstract session at American Society of Hematology (ASH) 2025 Annual Meeting. They were published simultaneously in The New England Journal of Medicine.

“[Tec-Dara in this setting] generated the greatest progression-free survival treatment effect to date [in RRMR] with a plateau phase after 6 months of therapy, suggesting potential for functional cure,” said Mateos, a consultant physician and associate professor at the University of Salamanca, Salamanca, Spain.

“We consider that this synergistic immunotherapy combination…is a new potential standard of care for relapsed or refractory multiple myeloma after at least on prior line of therapy, with broad potential across academic and community settings,” added Mateos, who also directs the Multiple Myeloma Program at the University.

Based on the MajesTEC-3 findings, the FDA proactively awarded a national priority voucher to Tec-Dara under the Commissioner’s National Priority Voucher pilot program designed to accelerate the review of certain promising products.

About Tec-Dara

Teclistamab (Tecvayli) is an off-the-shelf first-in-class bispecific monoclonal antibody shown in the MajesTEC-1 trial to provide deep, durable responses in RRMM, with improved efficacy and safety with earlier lines of therapy. The FDA approved the agent for use in 4th or greater lines of therapy in 2022 based on those findings.

Daratumumab (Darzalex) is a widely used anti-CD38 monoclonal antibody currently considered the SOC therapy for RRMM. Both agents are products of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Although front-line therapy for multiple myeloma has dramatically improved, there is a need for new, more effective treatment strategies in patients with disease progression, Mateos noted.

Therefore, she and her colleagues conducted MajesTEC-3, a randomized trial exploring the fully immunotherapy-based regimen of Tec-Dara vs daratumumab-based SOC in patients who had received one to three prior lines of therapy, including a proteasome inhibitor and lenalidomide (Len).

The study was the first to test a bispecific monoclonal antibody as early as the first relapse after initial treatment, she noted.

About MajesTEC-3

Study participants were 587 adults aged 25-88 years. Those with one prior line of therapy were required to be Len-refractory with progressive disease on or after the last therapy. Prior anti-CD-38 Patients with prior B-cell maturation antigen-directed therapy or who were refractory to anti-CD38 treatment were excluded.

The 291 patients randomized to the Tec-Dara treatment group and 296 randomized to the control group were treated in 28-day cycles according to the standard daratumumab schedule: weekly treatment during cycles 1 and 2, biweekly treatment during cycles 3-6, and monthly treatments beginning with cycle 7.

Teclistamab was initiated with an approved step-up dose school followed by 1.5 mg/kg weekly in cycles 1 and 2, 3 mg/kg biweekly in cycles 3-6, and 3 mg/kg monthly beginning with cycle 7.

The 36-month progression-free survival rates with Tec-Dara vs DPd/DVd were 83.4% and 29.7%, with the 36-month overall survival rates having been 83.3% and 65.0%. More than 90% of patients in the Tec-Dara group who were alive at 6 months were also alive at 30 months, Mateos noted.

For both progression-free survival and overall survival, the “clinically remarkable and statistically significant” differences were apparent across all prespecified and clinically relevant subgroups, she added. These included patients who were 75 years or older, Len-refractory patients, and those with high-risk cytogenetics, ≥ 60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposure.

Patients receiving Tec-Dara also had significantly higher rates of complete or better responses (81.8% vs 32.1%; odds ratio [OR], 9.56), overall response (89.0% vs 75.3%; OR, 2.65), and minimal residual disease-negativity (58.4% vs 17.1%; OR, 6.78).

The median time to first response and first complete or better response was similar in the two groups, but 36-month duration of response was 88.5 vs 36.4 months. At data cutoff, 49.4% of patients remained on study treatment — 71.0% in the Tec-Dara group and 28.3% in the DPd/DVd group, and median treatment duration was twice as long with Tec-Dara (32.4 vs 16.1 months), she said.

Serious adverse events occurred at similar rates in the treatment and control groups (70.7% and 62.4%) and most (44.2%) were grade 1 cytokine release syndrome (CRS). No grade 3 CRS occurred, and all CRS cases resolved.

Immune effector-cell-associated neurotoxicity occurred in 1.1% of patients, and all cases resolved.

Treatment-related adverse events leading to discontinuation occurred in 4.6% and 5.5% of patients in the Tec-Dara and DPd/DVd groups. The rates of deaths due to treatment-emergent adverse events were also similar in the groups (7.1% vs 5.9%).

Infections of any grade occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd patients, and grade 3/4 infections occurred in 54.1% and 43.4%. New-onset grade 3 or greater infections decreased over time.

“It’s important to acknowledge that patients with infections needed to be supported with adequate prophylaxis and immunoglobulins,” Mateo stressed.

Implications for Patients With RRMM

Teclistamab is currently only approved after three prior lines of therapy, but under the FDA Commissioner’s National Priority Voucher program, the agency will aim to complete its review of Tec-Dara for earlier treatment within 1-2 months following submission of an application for approval by Johnson & Johnson.

If an approval for that indication were to occur, it would be transformative for patients with RRMM, said Michael Rosenzweig, MD, of City of Hope, Duarte, California, in an interview with Medscape Medical News.

The [MajesTEC-3] findings suggest that Tec-Dar “really gives patients a chance at long-term disease control,” added Rosenzweig, chief of the Division of Multiple Myeloma, and an associate professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

MajesTEC-3 was funded by Johnson & Johnson. Mateos disclosed relationships with numerous pharmaceutical companies, including Johnson & Johnson. Rosenzweig reported consulting for Johnson & Johnson and was previously on the company’s speakers bureau.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and health care topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.

The National Institute for Health and Care Excellence (NICE) has recommended amivantamab (Rybrevant) plus lazertinib (Lazcluze) as a first-line option for adults with previously untreated advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.

In final draft guidance, NICE said the combination therapy should be funded by the NHS in England for eligible patients when it is the most appropriate option. Around 1115 people are expected to benefit.

Lung cancer is the third most common cancer and the leading cause of cancer mortality in the UK. It accounted for 10% of all new cancer diagnoses and 20% of cancer deaths in 2020. Approximately 31,000 people received NSCLC diagnoses in England in 2021, comprising 91% of all lung cancer cases. EGFR mutation-positive NSCLC is more common in women, non-smokers, and individuals from Asian ethnic backgrounds.

Welcoming the decision, Virginia Harrison, research trustee, EGFR+ UK, said, “This is a meaningful advance for patients and their families facing this diagnosis. [It] provides something the EGFR community urgently needs: more choice in first-line treatment.”

How Practice May Shift

The recommendation adds an alternative to existing standards, including osimertinib monotherapy or osimertinib plus pemetrexed/platinum-based chemotherapy. Clinical specialists noted that no single standard care exists for this patient group.

Younger patients and those willing to accept greater side effects may choose between amivantamab plus lazertinib or osimertinib plus chemotherapy. Patients older than 80 years might prefer osimertinib monotherapy due to adverse event considerations.

Mechanism of Action and Clinical Evidence

Amivantamab is a bispecific antibody that simultaneously binds EGFR and mesenchymal-epithelial transition receptors, blocking downstream signaling pathways that drive tumor growth and promoting immune-mediated cancer cell killing. Lazertinib is an oral third-generation EGFR TKI that selectively inhibits mutant EGFR signaling. Together, the agents provides complementary suppression of EGFR-driven tumour growth and resistance mechanisms.

The NICE recommendation is supported by results from the phase 3 MARIPOSA trial, which met its primary endpoint of progression-free survival (PFS). Treatment with amivantamab plus lazertinib significantly prolonged median PFS to 23.7 months compared with 16.6 months with osimertinib. The combination also demonstrated a significant improvement in overall survival, reducing the risk for death by 25% vs osimertinib. Median OS was not reached in the combination arm and was 36.7 months with osimertinib.

The most common adverse reactions with the combination included rash, nail toxicity, hypoalbuminaemia, hepatotoxicity, and stomatitis. 

A Medicines and Healthcare products Regulatory Agency-approved subcutaneous  formulation of amivantamab, authorized after the committee’s initial meeting, may further improve tolerability and convenience. Administration-related reactions occurred in 63% of patients with the intravenous formulation vs 14% with the subcutaneous formulation. Clinicians expect subcutaneous dosing to replace intravenous use in practice.

Dosing, Access, and Implementation

Amivantamab is administered every 2 weeks, either intravenously or subcutaneously. Lazertinib is taken as a daily oral tablet. 

Rybrevant costs £1079 for a 350-mg per 7-mL vial. Lazcluze is priced at £4128.50 for 56 x 80-mg tablets and £6192.75 for 28 x 240-mg tablets. Confidential NHS discounts are available through simple patient access schemes.

Integrated care boards, NHS England, and local authorities must implement the guidance within 90 days of publication. For drugs receiving positive draft recommendations for routine commissioning, interim funding becomes accessible from the Cancer Drugs Fund budget starting from the point of marketing authorisation or publication of draft guidance.

The National Institute for Health and Care Excellence (NICE) has recommended amivantamab (Rybrevant) plus lazertinib (Lazcluze) as a first-line option for adults with previously untreated advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.

In final draft guidance, NICE said the combination therapy should be funded by the NHS in England for eligible patients when it is the most appropriate option. Around 1115 people are expected to benefit.

Lung cancer is the third most common cancer and the leading cause of cancer mortality in the UK. It accounted for 10% of all new cancer diagnoses and 20% of cancer deaths in 2020. Approximately 31,000 people received NSCLC diagnoses in England in 2021, comprising 91% of all lung cancer cases. EGFR mutation-positive NSCLC is more common in women, non-smokers, and individuals from Asian ethnic backgrounds.

Welcoming the decision, Virginia Harrison, research trustee, EGFR+ UK, said, “This is a meaningful advance for patients and their families facing this diagnosis. [It] provides something the EGFR community urgently needs: more choice in first-line treatment.”

How Practice May Shift

The recommendation adds an alternative to existing standards, including osimertinib monotherapy or osimertinib plus pemetrexed/platinum-based chemotherapy. Clinical specialists noted that no single standard care exists for this patient group.

Younger patients and those willing to accept greater side effects may choose between amivantamab plus lazertinib or osimertinib plus chemotherapy. Patients older than 80 years might prefer osimertinib monotherapy due to adverse event considerations.

Mechanism of Action and Clinical Evidence

Amivantamab is a bispecific antibody that simultaneously binds EGFR and mesenchymal-epithelial transition receptors, blocking downstream signaling pathways that drive tumor growth and promoting immune-mediated cancer cell killing. Lazertinib is an oral third-generation EGFR TKI that selectively inhibits mutant EGFR signaling. Together, the agents provides complementary suppression of EGFR-driven tumour growth and resistance mechanisms.

The NICE recommendation is supported by results from the phase 3 MARIPOSA trial, which met its primary endpoint of progression-free survival (PFS). Treatment with amivantamab plus lazertinib significantly prolonged median PFS to 23.7 months compared with 16.6 months with osimertinib. The combination also demonstrated a significant improvement in overall survival, reducing the risk for death by 25% vs osimertinib. Median OS was not reached in the combination arm and was 36.7 months with osimertinib.

The most common adverse reactions with the combination included rash, nail toxicity, hypoalbuminaemia, hepatotoxicity, and stomatitis. 

A Medicines and Healthcare products Regulatory Agency-approved subcutaneous  formulation of amivantamab, authorized after the committee’s initial meeting, may further improve tolerability and convenience. Administration-related reactions occurred in 63% of patients with the intravenous formulation vs 14% with the subcutaneous formulation. Clinicians expect subcutaneous dosing to replace intravenous use in practice.

Dosing, Access, and Implementation

Amivantamab is administered every 2 weeks, either intravenously or subcutaneously. Lazertinib is taken as a daily oral tablet. 

Rybrevant costs £1079 for a 350-mg per 7-mL vial. Lazcluze is priced at £4128.50 for 56 x 80-mg tablets and £6192.75 for 28 x 240-mg tablets. Confidential NHS discounts are available through simple patient access schemes.

Integrated care boards, NHS England, and local authorities must implement the guidance within 90 days of publication. For drugs receiving positive draft recommendations for routine commissioning, interim funding becomes accessible from the Cancer Drugs Fund budget starting from the point of marketing authorisation or publication of draft guidance.

The National Institute for Health and Care Excellence (NICE) has recommended amivantamab (Rybrevant) plus lazertinib (Lazcluze) as a first-line option for adults with previously untreated advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.

In final draft guidance, NICE said the combination therapy should be funded by the NHS in England for eligible patients when it is the most appropriate option. Around 1115 people are expected to benefit.

Lung cancer is the third most common cancer and the leading cause of cancer mortality in the UK. It accounted for 10% of all new cancer diagnoses and 20% of cancer deaths in 2020. Approximately 31,000 people received NSCLC diagnoses in England in 2021, comprising 91% of all lung cancer cases. EGFR mutation-positive NSCLC is more common in women, non-smokers, and individuals from Asian ethnic backgrounds.

Welcoming the decision, Virginia Harrison, research trustee, EGFR+ UK, said, “This is a meaningful advance for patients and their families facing this diagnosis. [It] provides something the EGFR community urgently needs: more choice in first-line treatment.”

How Practice May Shift

The recommendation adds an alternative to existing standards, including osimertinib monotherapy or osimertinib plus pemetrexed/platinum-based chemotherapy. Clinical specialists noted that no single standard care exists for this patient group.

Younger patients and those willing to accept greater side effects may choose between amivantamab plus lazertinib or osimertinib plus chemotherapy. Patients older than 80 years might prefer osimertinib monotherapy due to adverse event considerations.

Mechanism of Action and Clinical Evidence

Amivantamab is a bispecific antibody that simultaneously binds EGFR and mesenchymal-epithelial transition receptors, blocking downstream signaling pathways that drive tumor growth and promoting immune-mediated cancer cell killing. Lazertinib is an oral third-generation EGFR TKI that selectively inhibits mutant EGFR signaling. Together, the agents provides complementary suppression of EGFR-driven tumour growth and resistance mechanisms.

The NICE recommendation is supported by results from the phase 3 MARIPOSA trial, which met its primary endpoint of progression-free survival (PFS). Treatment with amivantamab plus lazertinib significantly prolonged median PFS to 23.7 months compared with 16.6 months with osimertinib. The combination also demonstrated a significant improvement in overall survival, reducing the risk for death by 25% vs osimertinib. Median OS was not reached in the combination arm and was 36.7 months with osimertinib.

The most common adverse reactions with the combination included rash, nail toxicity, hypoalbuminaemia, hepatotoxicity, and stomatitis. 

A Medicines and Healthcare products Regulatory Agency-approved subcutaneous  formulation of amivantamab, authorized after the committee’s initial meeting, may further improve tolerability and convenience. Administration-related reactions occurred in 63% of patients with the intravenous formulation vs 14% with the subcutaneous formulation. Clinicians expect subcutaneous dosing to replace intravenous use in practice.

Dosing, Access, and Implementation

Amivantamab is administered every 2 weeks, either intravenously or subcutaneously. Lazertinib is taken as a daily oral tablet. 

Rybrevant costs £1079 for a 350-mg per 7-mL vial. Lazcluze is priced at £4128.50 for 56 x 80-mg tablets and £6192.75 for 28 x 240-mg tablets. Confidential NHS discounts are available through simple patient access schemes.

Integrated care boards, NHS England, and local authorities must implement the guidance within 90 days of publication. For drugs receiving positive draft recommendations for routine commissioning, interim funding becomes accessible from the Cancer Drugs Fund budget starting from the point of marketing authorisation or publication of draft guidance.

Intensive long-distance running could be a risk for advanced adenomas (AAs) for the colon, a small prospective study reported this summer at the American Society of Clinical Oncology (ASCO) 2025.

Refined screening strategies for this running population are therefore warranted, and pathologic and epidemiologic evaluations should explore causation and ancillary risk factors in this unique population, according to Timothy L. Cannon, MD, oncologist at Inova Schar Cancer Institute in Fairfax, Virginia, and colleagues.

The full study (NCT 05419531), which is currently being reviewed for publication, looked at colonoscopy results from 100 marathon and ultramarathon runners and found that almost half had polyps, and 15% (95% CI, 7.9-22.4) had confirmed AAs).

The AA rate was higher than the 4.5% to 6% seen in adults in their late 40s in the general population and was higher even than the 12% found in Alaska Natives, who are at heightened risk for colon cancer.

"After meeting 3 extreme endurance athletes — 2 who ran 100-mile ultramarathons and 1 lady who ran dozens of triathlons — with stage IV colon cancer before age 40, I began to be suspicious of a link," Cannon told Medscape Medical News. At least 2 of them said they were told that bleeding after long runs was common, which they took to mean as normal. "I could imagine multiple reasons that endurance runners would be predisposed to cancer, with my initial focus on the inflammation and cell turnover incited by the well-described ischemia and runner's colitis."

Study Details

From October 2022 to December 2024, 100 eligible participants aged 35 to 50 years had colonoscopies. The median age was 42.5 years; 55 participants were female and 45 were male. In terms of endurance eligibility, all had completed at ≥ 2 registered ultramarathons (50 km or longer) or 5 registered marathons (26.2 miles). Patients were excluded if they were known or suspected to have inflammatory bowel disease, familial adenomatous polyposis, or Lynch syndrome (hereditary nonpolyposis colorectal cancer).

The historical 1.2% in average-risk individuals aged 40-49 years was used for the expected rate of AAs, defined as lesions > 10 mm, lesions with 25% tubulovillous features, or high-grade dysplasia.

In other findings, 39 had ≥ 1 adenoma and had ≥ 3 adenomas but did not meet AA criteria and were not included in the 15% with AA.

While no colon cancer was detected in the cohort, Cannon said 30% experienced rectal bleeding after exercise, especially those with AAs compared with those without: 53% vs 22%. "While rectal bleeding had a significant association with finding advanced adenomas on the colonoscopy, there were still many with advanced adenomas who reported no bleeding," he said.

Runner's colitis, or trots, is a common condition thought to be related to ischemia, mechanical stress, or adverse impact on the gut microbiome. "Mechanism is the huge question that I certainly can't answer at this point," Cannon said. "At some distance, blood flow gets diverted from the splanchnic circulation to the legs, and gut ischemia seems to ensue. I envision high rates of disorderly cell turnover and more opportunities for mutagenesis. This needs to be studied, and what I am describing is certainly either an oversimplification or simply not related at all."

The authors noted that exercise-induced gastrointestinal injury is likely associated with reduced blood flow to the intestines during long-distance running, but not evidence has linked this bowel ischemia to carcinogenesis.

Diet could be another factor. "I am fascinated with runners' diets. They seem to consume, on average, a huge amount of ultraprocessed bars and goos. They also may drink from plastic bottles far more than the average person. These are just 2 of many possibilities," Cannon said. "Nearly a third of our participants were vegan or vegetarian. We are planning a second, more detailed, survey or our participants. We will really dig down on these questions as well as specifics regarding their training regimens."

Commenting on the study but not involved in it, Thomas F. Imperiale, MD, professor of gastroenterology and hepatology at Indiana University Indianapolis, said that while the findings are provocative, several methodological issues require consideration in subsequent research.

"First, the comparative benchmark of advanced adenoma prevalence of 1.2% is based on screening colonoscopy data from 25 years ago. At the very least, a concurrent benchmark should be used," he told Medscape Medical News. The second issue is the absence of a control group of persons who may exercise but who do not run marathons. "This addition would strengthen study validity more than using a concurrent comparison."

The case group of long-distance runners and a control group of nonmarathon runners could be compared for prevalence of AAs with adjustment for age, sex, race or ethnicity, family history of colorectal cancer, diet, other physical activity, tobacco use history, BMI or waist circumference, ethanol use, and perhaps other early-life exposures and indication for colonoscopy. "Last, it would be interesting to know whether and how often the 100 participants developed symptoms possibly consistent with colonic ischemia either during or after long-distance runs, which might provide indirect support for the presumptive mechanism of action."

In other comments, Hamed Khalili, MD, MPH, gastroenterologist at Massachusetts General Hospital and associate professor at Harvard Medical School, both in Boston, called the results very preliminary. "The sample size is small, and the comparator group is a historical control, so it's unclear whether the observed differences are just a sampling issue," he said.

Cannon has this advice for physicians: "Please don't dismiss symptoms of runner's colitis as benign. This condition requires investigation," he said. While he hasn't seen any expert recommendation to treat postrunning bleeding any differently from other causes of melena or hematochezia, both of which would normally merit a colonoscopy, in practice many gastroenterologists dismiss this type of bleeding as benign. "If larger studies confirm our findings, I don't think it's out of the question that marathoners will have unique screening recommendations. But this study is not robust enough, of course, to merit such a recommendation."

His group is planning a study on the runner's microbiome and on the proteome of the colonic tissue in this group.

Cannon reported having no relevant conflicts of interest to disclose. Imperiale and Khalili reported having no conflicts of interest relevant to their comments on the study.

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

Intensive long-distance running could be a risk for advanced adenomas (AAs) for the colon, a small prospective study reported this summer at the American Society of Clinical Oncology (ASCO) 2025.

Refined screening strategies for this running population are therefore warranted, and pathologic and epidemiologic evaluations should explore causation and ancillary risk factors in this unique population, according to Timothy L. Cannon, MD, oncologist at Inova Schar Cancer Institute in Fairfax, Virginia, and colleagues.

The full study (NCT 05419531), which is currently being reviewed for publication, looked at colonoscopy results from 100 marathon and ultramarathon runners and found that almost half had polyps, and 15% (95% CI, 7.9-22.4) had confirmed AAs).

The AA rate was higher than the 4.5% to 6% seen in adults in their late 40s in the general population and was higher even than the 12% found in Alaska Natives, who are at heightened risk for colon cancer.

"After meeting 3 extreme endurance athletes — 2 who ran 100-mile ultramarathons and 1 lady who ran dozens of triathlons — with stage IV colon cancer before age 40, I began to be suspicious of a link," Cannon told Medscape Medical News. At least 2 of them said they were told that bleeding after long runs was common, which they took to mean as normal. "I could imagine multiple reasons that endurance runners would be predisposed to cancer, with my initial focus on the inflammation and cell turnover incited by the well-described ischemia and runner's colitis."

Study Details

From October 2022 to December 2024, 100 eligible participants aged 35 to 50 years had colonoscopies. The median age was 42.5 years; 55 participants were female and 45 were male. In terms of endurance eligibility, all had completed at ≥ 2 registered ultramarathons (50 km or longer) or 5 registered marathons (26.2 miles). Patients were excluded if they were known or suspected to have inflammatory bowel disease, familial adenomatous polyposis, or Lynch syndrome (hereditary nonpolyposis colorectal cancer).

The historical 1.2% in average-risk individuals aged 40-49 years was used for the expected rate of AAs, defined as lesions > 10 mm, lesions with 25% tubulovillous features, or high-grade dysplasia.

In other findings, 39 had ≥ 1 adenoma and had ≥ 3 adenomas but did not meet AA criteria and were not included in the 15% with AA.

While no colon cancer was detected in the cohort, Cannon said 30% experienced rectal bleeding after exercise, especially those with AAs compared with those without: 53% vs 22%. "While rectal bleeding had a significant association with finding advanced adenomas on the colonoscopy, there were still many with advanced adenomas who reported no bleeding," he said.

Runner's colitis, or trots, is a common condition thought to be related to ischemia, mechanical stress, or adverse impact on the gut microbiome. "Mechanism is the huge question that I certainly can't answer at this point," Cannon said. "At some distance, blood flow gets diverted from the splanchnic circulation to the legs, and gut ischemia seems to ensue. I envision high rates of disorderly cell turnover and more opportunities for mutagenesis. This needs to be studied, and what I am describing is certainly either an oversimplification or simply not related at all."

The authors noted that exercise-induced gastrointestinal injury is likely associated with reduced blood flow to the intestines during long-distance running, but not evidence has linked this bowel ischemia to carcinogenesis.

Diet could be another factor. "I am fascinated with runners' diets. They seem to consume, on average, a huge amount of ultraprocessed bars and goos. They also may drink from plastic bottles far more than the average person. These are just 2 of many possibilities," Cannon said. "Nearly a third of our participants were vegan or vegetarian. We are planning a second, more detailed, survey or our participants. We will really dig down on these questions as well as specifics regarding their training regimens."

Commenting on the study but not involved in it, Thomas F. Imperiale, MD, professor of gastroenterology and hepatology at Indiana University Indianapolis, said that while the findings are provocative, several methodological issues require consideration in subsequent research.

"First, the comparative benchmark of advanced adenoma prevalence of 1.2% is based on screening colonoscopy data from 25 years ago. At the very least, a concurrent benchmark should be used," he told Medscape Medical News. The second issue is the absence of a control group of persons who may exercise but who do not run marathons. "This addition would strengthen study validity more than using a concurrent comparison."

The case group of long-distance runners and a control group of nonmarathon runners could be compared for prevalence of AAs with adjustment for age, sex, race or ethnicity, family history of colorectal cancer, diet, other physical activity, tobacco use history, BMI or waist circumference, ethanol use, and perhaps other early-life exposures and indication for colonoscopy. "Last, it would be interesting to know whether and how often the 100 participants developed symptoms possibly consistent with colonic ischemia either during or after long-distance runs, which might provide indirect support for the presumptive mechanism of action."

In other comments, Hamed Khalili, MD, MPH, gastroenterologist at Massachusetts General Hospital and associate professor at Harvard Medical School, both in Boston, called the results very preliminary. "The sample size is small, and the comparator group is a historical control, so it's unclear whether the observed differences are just a sampling issue," he said.

Cannon has this advice for physicians: "Please don't dismiss symptoms of runner's colitis as benign. This condition requires investigation," he said. While he hasn't seen any expert recommendation to treat postrunning bleeding any differently from other causes of melena or hematochezia, both of which would normally merit a colonoscopy, in practice many gastroenterologists dismiss this type of bleeding as benign. "If larger studies confirm our findings, I don't think it's out of the question that marathoners will have unique screening recommendations. But this study is not robust enough, of course, to merit such a recommendation."

His group is planning a study on the runner's microbiome and on the proteome of the colonic tissue in this group.

Cannon reported having no relevant conflicts of interest to disclose. Imperiale and Khalili reported having no conflicts of interest relevant to their comments on the study.

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

Intensive long-distance running could be a risk for advanced adenomas (AAs) for the colon, a small prospective study reported this summer at the American Society of Clinical Oncology (ASCO) 2025.

Refined screening strategies for this running population are therefore warranted, and pathologic and epidemiologic evaluations should explore causation and ancillary risk factors in this unique population, according to Timothy L. Cannon, MD, oncologist at Inova Schar Cancer Institute in Fairfax, Virginia, and colleagues.

The full study (NCT 05419531), which is currently being reviewed for publication, looked at colonoscopy results from 100 marathon and ultramarathon runners and found that almost half had polyps, and 15% (95% CI, 7.9-22.4) had confirmed AAs).

The AA rate was higher than the 4.5% to 6% seen in adults in their late 40s in the general population and was higher even than the 12% found in Alaska Natives, who are at heightened risk for colon cancer.

"After meeting 3 extreme endurance athletes — 2 who ran 100-mile ultramarathons and 1 lady who ran dozens of triathlons — with stage IV colon cancer before age 40, I began to be suspicious of a link," Cannon told Medscape Medical News. At least 2 of them said they were told that bleeding after long runs was common, which they took to mean as normal. "I could imagine multiple reasons that endurance runners would be predisposed to cancer, with my initial focus on the inflammation and cell turnover incited by the well-described ischemia and runner's colitis."

Study Details

From October 2022 to December 2024, 100 eligible participants aged 35 to 50 years had colonoscopies. The median age was 42.5 years; 55 participants were female and 45 were male. In terms of endurance eligibility, all had completed at ≥ 2 registered ultramarathons (50 km or longer) or 5 registered marathons (26.2 miles). Patients were excluded if they were known or suspected to have inflammatory bowel disease, familial adenomatous polyposis, or Lynch syndrome (hereditary nonpolyposis colorectal cancer).

The historical 1.2% in average-risk individuals aged 40-49 years was used for the expected rate of AAs, defined as lesions > 10 mm, lesions with 25% tubulovillous features, or high-grade dysplasia.

In other findings, 39 had ≥ 1 adenoma and had ≥ 3 adenomas but did not meet AA criteria and were not included in the 15% with AA.

While no colon cancer was detected in the cohort, Cannon said 30% experienced rectal bleeding after exercise, especially those with AAs compared with those without: 53% vs 22%. "While rectal bleeding had a significant association with finding advanced adenomas on the colonoscopy, there were still many with advanced adenomas who reported no bleeding," he said.

Runner's colitis, or trots, is a common condition thought to be related to ischemia, mechanical stress, or adverse impact on the gut microbiome. "Mechanism is the huge question that I certainly can't answer at this point," Cannon said. "At some distance, blood flow gets diverted from the splanchnic circulation to the legs, and gut ischemia seems to ensue. I envision high rates of disorderly cell turnover and more opportunities for mutagenesis. This needs to be studied, and what I am describing is certainly either an oversimplification or simply not related at all."

The authors noted that exercise-induced gastrointestinal injury is likely associated with reduced blood flow to the intestines during long-distance running, but not evidence has linked this bowel ischemia to carcinogenesis.

Diet could be another factor. "I am fascinated with runners' diets. They seem to consume, on average, a huge amount of ultraprocessed bars and goos. They also may drink from plastic bottles far more than the average person. These are just 2 of many possibilities," Cannon said. "Nearly a third of our participants were vegan or vegetarian. We are planning a second, more detailed, survey or our participants. We will really dig down on these questions as well as specifics regarding their training regimens."

Commenting on the study but not involved in it, Thomas F. Imperiale, MD, professor of gastroenterology and hepatology at Indiana University Indianapolis, said that while the findings are provocative, several methodological issues require consideration in subsequent research.

"First, the comparative benchmark of advanced adenoma prevalence of 1.2% is based on screening colonoscopy data from 25 years ago. At the very least, a concurrent benchmark should be used," he told Medscape Medical News. The second issue is the absence of a control group of persons who may exercise but who do not run marathons. "This addition would strengthen study validity more than using a concurrent comparison."

The case group of long-distance runners and a control group of nonmarathon runners could be compared for prevalence of AAs with adjustment for age, sex, race or ethnicity, family history of colorectal cancer, diet, other physical activity, tobacco use history, BMI or waist circumference, ethanol use, and perhaps other early-life exposures and indication for colonoscopy. "Last, it would be interesting to know whether and how often the 100 participants developed symptoms possibly consistent with colonic ischemia either during or after long-distance runs, which might provide indirect support for the presumptive mechanism of action."

In other comments, Hamed Khalili, MD, MPH, gastroenterologist at Massachusetts General Hospital and associate professor at Harvard Medical School, both in Boston, called the results very preliminary. "The sample size is small, and the comparator group is a historical control, so it's unclear whether the observed differences are just a sampling issue," he said.

Cannon has this advice for physicians: "Please don't dismiss symptoms of runner's colitis as benign. This condition requires investigation," he said. While he hasn't seen any expert recommendation to treat postrunning bleeding any differently from other causes of melena or hematochezia, both of which would normally merit a colonoscopy, in practice many gastroenterologists dismiss this type of bleeding as benign. "If larger studies confirm our findings, I don't think it's out of the question that marathoners will have unique screening recommendations. But this study is not robust enough, of course, to merit such a recommendation."

His group is planning a study on the runner's microbiome and on the proteome of the colonic tissue in this group.

Cannon reported having no relevant conflicts of interest to disclose. Imperiale and Khalili reported having no conflicts of interest relevant to their comments on the study.

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

Neuropathic pain in individuals with cancer remains a challenging clinical problem that requires advanced pharmacologic skills and a clear understanding of the molecular mechanisms that drive it.

At the 32nd Annual Congress of the Italian Society of Palliative Care, 3 experts outlined an updated framework that begins with basic biology and leads to the most appropriate therapeutic choice.
 

Fibre Reprogramming

Diego Maria Michele Fornasari, professor of pharmacology and director of the Postgraduate School of Specialization in Pharmacology and Clinical Toxicology at the University of Milan, Milan, Italy, outlined how a healthy nerve fibre becomes chronically hyperexcitable.

“The pathogenic mechanisms of pain, even though we experience hundreds of different pains, can be counted on the fingers of one hand,” he said.

In oncology, nerve injury caused by tumour compression, chemotherapy, or radiotherapy initiates a molecular cascade that reshapes the nerve fibre.

“The injured area is reprogrammed because the neuron attempts to regenerate, and to regenerate it must express proteins seen during embryonic life,” Fornasari said.

This process leads to the appearance of embryonic sodium channels (particularly Nav1.3), which impart abnormally high electrical activity to neurones.

The second mechanism involves the loss of a protective physiologic feature, namely, intermittent failure of signal conduction. Under normal conditions, occasional conduction failures reduce pain intensity. In neuropathic pain, overexpression of hyperpolarisation–activated cyclic nucleotide-gated channels, the same channels that govern sinoatrial node automaticity, makes the neuron hyperexcitable and unable to modulate transmission. The result is that “all stimuli reach the spinal cord and the central nervous system.”

Fornasari illustrated the concerns regarding pain in bone metastases. “The tumour cell is an intelligent cell, capable of producing substances that can interfere with nociceptive mechanisms,” he said.

He also highlighted the mechanisms of pain in patients with bone metastases. Prostate cancer cells that metastasised to the bone that produce tumour cells produce large amounts of nerve growth factor, which does not promote growth in adult neurones but causes hypertrophy and sprouting of nerve fibres. “Each of these ‘spikes’ is actually a neuropathic lesion of the fibre,” Fornasari explained, clarifying how this mechanism contributes to the often-devastating intensity of pain from bone metastases.
 

Diagnostic Precision

Francesca Dina Ricchini, oncologist and palliative care specialist working in the Palliative Care Unit at the National Cancer Institute in Milan, Italy, addressed the translation of molecular knowledge into clinical diagnosis. “It is very important to be able to translate these concepts into diagnostic tools,” she said.

Neuropathic involvement affects approximately 40% of individuals with cancer, with 20% presenting with pure neuropathic pain and another 20% with mixed pain.

Approximately 75% of cases are related to the disease itself, and the remainder are related to oncologic treatments. Despite its prevalence, neuropathic pain remains underdiagnosed, contributing to suboptimal analgesia and an impaired quality of life.

Screening tools such as PainDETECT, DN4, and the LANSS scale can support assessment, but Ricchini cautioned that “they are tools that can be used as aids but do not make a diagnosis on their own and have not been validated in oncology patients.”

She noted that quantitative sensory testing (QST) complements clinical judgement by quantifying sensory thresholds for thermal, mechanical, and pain stimuli, aiding in the identification of neuropathic pain mechanisms, particularly in oncology settings. QST can complement clinical judgement and diagnostic algorithms developed by the International Association for the Study of Pain to help clinicians systematically identify neuropathic components.

“The key is to start from symptoms, what the patient tells us,” Ricchini added.

However, bedside assessments remain essential. Simple tool needles, cotton, and the clinician’s thumb allow the evaluation of hyperalgesia, allodynia, and other neuropathic features of the affected area. With careful history taking and physical examination, clinicians can often reach an accurate diagnosis without complex testing.
 

Opioid Use

Sebastiano Mercadante, director of the Anesthesia & Intensive Care and Pain Relief and Supportive Care Unit in La Maddalena Cancer Center Palermo at the University of Palermo in Palermo, Italy, discussed opioid therapy in neuropathic pain. “Responsiveness to opioid drugs varies from patient to patient,” he said.

Opioids develop tolerance and have a ceiling effect that is driven by adverse events. Mercadante emphasised the need to “optimise their use” by staying within the therapeutic window where the benefits outweigh the harm.

Responsiveness depends on genetic polymorphisms affecting receptors and metabolism, pain patterns, age, sex, and psychological distress. “Those with the worst response are patients with significant psychological distress,” he noted.

The opioid escalation index helps to stratify patients. Slow escalation predicts a better prognosis, whereas rapid escalation should prompt specialist involvement and evaluation of factors such as delirium, anxiety, and depression in patients.
 

Drug Strategies

Switching opioids can be helpful when they become less effective. Mercadante explained that switching opioids “can facilitate receptor internalisation, excluding from continuous stimulation,” allowing “receptor refreshing” and allowing an overstimulated system to be cleared and restoring analgesia. Switching to methadone, when conducted by experienced clinicians, often yields substantial benefits for patients.

Fornasari clarified the mechanisms of action of gabapentinoids, which act on the alpha-2-delta subunit of calcium channels by restoring normal channel numbers rather than by closing them. This distinction is important because it is a slow mechanism that requires approximately 2 weeks for full effect, which is crucial information for clinicians who often discontinue treatment prematurely after a few days of treatment.

Antidepressants, including amitriptyline and serotonin-norepinephrine reuptake inhibitors such as duloxetine, strengthen descending inhibitory pathways by increasing serotonin and noradrenaline levels.

Fornasari also mentioned desvenlafaxine, the active metabolite of venlafaxine, which “has greater activity on descending noradrenergic pathways” and could be particularly useful when the predominant component is noradrenergic.
 

Topical Options

Capsaicin is an option for chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced neuropathy, the expert explained, is related to the overexpression of transient receptor potential cation channel subfamily V member 1, also known as the capsaicin receptor. Topical capsaicin abnormally stimulates these receptors, causing a massive influx of calcium that “defunctionalises the fibre” for periods ranging from a week to 2 months.
 

Clinical Takeaways

Therefore, neuropathic pain, particularly in patients with cancer, requires a multimodal approach that begins with an understanding of the molecular mechanisms to develop personalised treatment options. As Fornasari concluded, “Often, a lack of knowledge of a drug’s mechanism of action leads to its inappropriate, and ultimately ineffective, use.” The challenge for clinicians is to translate this knowledge into tangible improvements for patients, remembering that each patient is unique and requires personalised care that goes beyond standardised protocols.

Clinicians aim to translate these insights into meaningful relief, recognising that each patient requires tailored care.
 

Practical Guidance

• Accurate diagnosis: Screening tools should only be used as support, and decisions should be on the basis of a detailed history and physical examination. In individuals with cancer, the interview always began with the patient’s account.
• Recognising negative prognostic factors: Neuropathic pain, incident pain, psychological distress, delirium, and unrealistic expectations indicate a more difficult course and require a more intensive approach.
• Opioids should be used wisely: Dose escalation should be monitored, rotation should be considered when needed, and psychological factors should be assessed throughout care. As experts have noted, clinicians should try at least 2 or 3 opioids and at least 2 routes of administration before considering invasive procedures.
• Integrating adjuvant medicines early: Gabapentin and other antidepressants are not third-line treatments for individuals with cancer. Adequately dosed for at least 2 weeks to allow therapeutic benefit.
• Consider topical options: In localised peripheral neuropathies, capsaicin can be a valid addition to treatment.
• Use of non-opioid medicines: Some individuals respond exceptionally well to anti-inflammatory agents, with effects that can match those of high morphine doses.

This story was translated from Univadis Italy, part of the this news organization Professional Network.

A version of this article appeared on Medscape.com.

Neuropathic pain in individuals with cancer remains a challenging clinical problem that requires advanced pharmacologic skills and a clear understanding of the molecular mechanisms that drive it.

At the 32nd Annual Congress of the Italian Society of Palliative Care, 3 experts outlined an updated framework that begins with basic biology and leads to the most appropriate therapeutic choice.
 

Fibre Reprogramming

Diego Maria Michele Fornasari, professor of pharmacology and director of the Postgraduate School of Specialization in Pharmacology and Clinical Toxicology at the University of Milan, Milan, Italy, outlined how a healthy nerve fibre becomes chronically hyperexcitable.

“The pathogenic mechanisms of pain, even though we experience hundreds of different pains, can be counted on the fingers of one hand,” he said.

In oncology, nerve injury caused by tumour compression, chemotherapy, or radiotherapy initiates a molecular cascade that reshapes the nerve fibre.

“The injured area is reprogrammed because the neuron attempts to regenerate, and to regenerate it must express proteins seen during embryonic life,” Fornasari said.

This process leads to the appearance of embryonic sodium channels (particularly Nav1.3), which impart abnormally high electrical activity to neurones.

The second mechanism involves the loss of a protective physiologic feature, namely, intermittent failure of signal conduction. Under normal conditions, occasional conduction failures reduce pain intensity. In neuropathic pain, overexpression of hyperpolarisation–activated cyclic nucleotide-gated channels, the same channels that govern sinoatrial node automaticity, makes the neuron hyperexcitable and unable to modulate transmission. The result is that “all stimuli reach the spinal cord and the central nervous system.”

Fornasari illustrated the concerns regarding pain in bone metastases. “The tumour cell is an intelligent cell, capable of producing substances that can interfere with nociceptive mechanisms,” he said.

He also highlighted the mechanisms of pain in patients with bone metastases. Prostate cancer cells that metastasised to the bone that produce tumour cells produce large amounts of nerve growth factor, which does not promote growth in adult neurones but causes hypertrophy and sprouting of nerve fibres. “Each of these ‘spikes’ is actually a neuropathic lesion of the fibre,” Fornasari explained, clarifying how this mechanism contributes to the often-devastating intensity of pain from bone metastases.
 

Diagnostic Precision

Francesca Dina Ricchini, oncologist and palliative care specialist working in the Palliative Care Unit at the National Cancer Institute in Milan, Italy, addressed the translation of molecular knowledge into clinical diagnosis. “It is very important to be able to translate these concepts into diagnostic tools,” she said.

Neuropathic involvement affects approximately 40% of individuals with cancer, with 20% presenting with pure neuropathic pain and another 20% with mixed pain.

Approximately 75% of cases are related to the disease itself, and the remainder are related to oncologic treatments. Despite its prevalence, neuropathic pain remains underdiagnosed, contributing to suboptimal analgesia and an impaired quality of life.

Screening tools such as PainDETECT, DN4, and the LANSS scale can support assessment, but Ricchini cautioned that “they are tools that can be used as aids but do not make a diagnosis on their own and have not been validated in oncology patients.”

She noted that quantitative sensory testing (QST) complements clinical judgement by quantifying sensory thresholds for thermal, mechanical, and pain stimuli, aiding in the identification of neuropathic pain mechanisms, particularly in oncology settings. QST can complement clinical judgement and diagnostic algorithms developed by the International Association for the Study of Pain to help clinicians systematically identify neuropathic components.

“The key is to start from symptoms, what the patient tells us,” Ricchini added.

However, bedside assessments remain essential. Simple tool needles, cotton, and the clinician’s thumb allow the evaluation of hyperalgesia, allodynia, and other neuropathic features of the affected area. With careful history taking and physical examination, clinicians can often reach an accurate diagnosis without complex testing.
 

Opioid Use

Sebastiano Mercadante, director of the Anesthesia & Intensive Care and Pain Relief and Supportive Care Unit in La Maddalena Cancer Center Palermo at the University of Palermo in Palermo, Italy, discussed opioid therapy in neuropathic pain. “Responsiveness to opioid drugs varies from patient to patient,” he said.

Opioids develop tolerance and have a ceiling effect that is driven by adverse events. Mercadante emphasised the need to “optimise their use” by staying within the therapeutic window where the benefits outweigh the harm.

Responsiveness depends on genetic polymorphisms affecting receptors and metabolism, pain patterns, age, sex, and psychological distress. “Those with the worst response are patients with significant psychological distress,” he noted.

The opioid escalation index helps to stratify patients. Slow escalation predicts a better prognosis, whereas rapid escalation should prompt specialist involvement and evaluation of factors such as delirium, anxiety, and depression in patients.
 

Drug Strategies

Switching opioids can be helpful when they become less effective. Mercadante explained that switching opioids “can facilitate receptor internalisation, excluding from continuous stimulation,” allowing “receptor refreshing” and allowing an overstimulated system to be cleared and restoring analgesia. Switching to methadone, when conducted by experienced clinicians, often yields substantial benefits for patients.

Fornasari clarified the mechanisms of action of gabapentinoids, which act on the alpha-2-delta subunit of calcium channels by restoring normal channel numbers rather than by closing them. This distinction is important because it is a slow mechanism that requires approximately 2 weeks for full effect, which is crucial information for clinicians who often discontinue treatment prematurely after a few days of treatment.

Antidepressants, including amitriptyline and serotonin-norepinephrine reuptake inhibitors such as duloxetine, strengthen descending inhibitory pathways by increasing serotonin and noradrenaline levels.

Fornasari also mentioned desvenlafaxine, the active metabolite of venlafaxine, which “has greater activity on descending noradrenergic pathways” and could be particularly useful when the predominant component is noradrenergic.
 

Topical Options

Capsaicin is an option for chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced neuropathy, the expert explained, is related to the overexpression of transient receptor potential cation channel subfamily V member 1, also known as the capsaicin receptor. Topical capsaicin abnormally stimulates these receptors, causing a massive influx of calcium that “defunctionalises the fibre” for periods ranging from a week to 2 months.
 

Clinical Takeaways

Therefore, neuropathic pain, particularly in patients with cancer, requires a multimodal approach that begins with an understanding of the molecular mechanisms to develop personalised treatment options. As Fornasari concluded, “Often, a lack of knowledge of a drug’s mechanism of action leads to its inappropriate, and ultimately ineffective, use.” The challenge for clinicians is to translate this knowledge into tangible improvements for patients, remembering that each patient is unique and requires personalised care that goes beyond standardised protocols.

Clinicians aim to translate these insights into meaningful relief, recognising that each patient requires tailored care.
 

Practical Guidance

• Accurate diagnosis: Screening tools should only be used as support, and decisions should be on the basis of a detailed history and physical examination. In individuals with cancer, the interview always began with the patient’s account.
• Recognising negative prognostic factors: Neuropathic pain, incident pain, psychological distress, delirium, and unrealistic expectations indicate a more difficult course and require a more intensive approach.
• Opioids should be used wisely: Dose escalation should be monitored, rotation should be considered when needed, and psychological factors should be assessed throughout care. As experts have noted, clinicians should try at least 2 or 3 opioids and at least 2 routes of administration before considering invasive procedures.
• Integrating adjuvant medicines early: Gabapentin and other antidepressants are not third-line treatments for individuals with cancer. Adequately dosed for at least 2 weeks to allow therapeutic benefit.
• Consider topical options: In localised peripheral neuropathies, capsaicin can be a valid addition to treatment.
• Use of non-opioid medicines: Some individuals respond exceptionally well to anti-inflammatory agents, with effects that can match those of high morphine doses.

This story was translated from Univadis Italy, part of the this news organization Professional Network.

A version of this article appeared on Medscape.com.

Neuropathic pain in individuals with cancer remains a challenging clinical problem that requires advanced pharmacologic skills and a clear understanding of the molecular mechanisms that drive it.

At the 32nd Annual Congress of the Italian Society of Palliative Care, 3 experts outlined an updated framework that begins with basic biology and leads to the most appropriate therapeutic choice.
 

Fibre Reprogramming

Diego Maria Michele Fornasari, professor of pharmacology and director of the Postgraduate School of Specialization in Pharmacology and Clinical Toxicology at the University of Milan, Milan, Italy, outlined how a healthy nerve fibre becomes chronically hyperexcitable.

“The pathogenic mechanisms of pain, even though we experience hundreds of different pains, can be counted on the fingers of one hand,” he said.

In oncology, nerve injury caused by tumour compression, chemotherapy, or radiotherapy initiates a molecular cascade that reshapes the nerve fibre.

“The injured area is reprogrammed because the neuron attempts to regenerate, and to regenerate it must express proteins seen during embryonic life,” Fornasari said.

This process leads to the appearance of embryonic sodium channels (particularly Nav1.3), which impart abnormally high electrical activity to neurones.

The second mechanism involves the loss of a protective physiologic feature, namely, intermittent failure of signal conduction. Under normal conditions, occasional conduction failures reduce pain intensity. In neuropathic pain, overexpression of hyperpolarisation–activated cyclic nucleotide-gated channels, the same channels that govern sinoatrial node automaticity, makes the neuron hyperexcitable and unable to modulate transmission. The result is that “all stimuli reach the spinal cord and the central nervous system.”

Fornasari illustrated the concerns regarding pain in bone metastases. “The tumour cell is an intelligent cell, capable of producing substances that can interfere with nociceptive mechanisms,” he said.

He also highlighted the mechanisms of pain in patients with bone metastases. Prostate cancer cells that metastasised to the bone that produce tumour cells produce large amounts of nerve growth factor, which does not promote growth in adult neurones but causes hypertrophy and sprouting of nerve fibres. “Each of these ‘spikes’ is actually a neuropathic lesion of the fibre,” Fornasari explained, clarifying how this mechanism contributes to the often-devastating intensity of pain from bone metastases.
 

Diagnostic Precision

Francesca Dina Ricchini, oncologist and palliative care specialist working in the Palliative Care Unit at the National Cancer Institute in Milan, Italy, addressed the translation of molecular knowledge into clinical diagnosis. “It is very important to be able to translate these concepts into diagnostic tools,” she said.

Neuropathic involvement affects approximately 40% of individuals with cancer, with 20% presenting with pure neuropathic pain and another 20% with mixed pain.

Approximately 75% of cases are related to the disease itself, and the remainder are related to oncologic treatments. Despite its prevalence, neuropathic pain remains underdiagnosed, contributing to suboptimal analgesia and an impaired quality of life.

Screening tools such as PainDETECT, DN4, and the LANSS scale can support assessment, but Ricchini cautioned that “they are tools that can be used as aids but do not make a diagnosis on their own and have not been validated in oncology patients.”

She noted that quantitative sensory testing (QST) complements clinical judgement by quantifying sensory thresholds for thermal, mechanical, and pain stimuli, aiding in the identification of neuropathic pain mechanisms, particularly in oncology settings. QST can complement clinical judgement and diagnostic algorithms developed by the International Association for the Study of Pain to help clinicians systematically identify neuropathic components.

“The key is to start from symptoms, what the patient tells us,” Ricchini added.

However, bedside assessments remain essential. Simple tool needles, cotton, and the clinician’s thumb allow the evaluation of hyperalgesia, allodynia, and other neuropathic features of the affected area. With careful history taking and physical examination, clinicians can often reach an accurate diagnosis without complex testing.
 

Opioid Use

Sebastiano Mercadante, director of the Anesthesia & Intensive Care and Pain Relief and Supportive Care Unit in La Maddalena Cancer Center Palermo at the University of Palermo in Palermo, Italy, discussed opioid therapy in neuropathic pain. “Responsiveness to opioid drugs varies from patient to patient,” he said.

Opioids develop tolerance and have a ceiling effect that is driven by adverse events. Mercadante emphasised the need to “optimise their use” by staying within the therapeutic window where the benefits outweigh the harm.

Responsiveness depends on genetic polymorphisms affecting receptors and metabolism, pain patterns, age, sex, and psychological distress. “Those with the worst response are patients with significant psychological distress,” he noted.

The opioid escalation index helps to stratify patients. Slow escalation predicts a better prognosis, whereas rapid escalation should prompt specialist involvement and evaluation of factors such as delirium, anxiety, and depression in patients.
 

Drug Strategies

Switching opioids can be helpful when they become less effective. Mercadante explained that switching opioids “can facilitate receptor internalisation, excluding from continuous stimulation,” allowing “receptor refreshing” and allowing an overstimulated system to be cleared and restoring analgesia. Switching to methadone, when conducted by experienced clinicians, often yields substantial benefits for patients.

Fornasari clarified the mechanisms of action of gabapentinoids, which act on the alpha-2-delta subunit of calcium channels by restoring normal channel numbers rather than by closing them. This distinction is important because it is a slow mechanism that requires approximately 2 weeks for full effect, which is crucial information for clinicians who often discontinue treatment prematurely after a few days of treatment.

Antidepressants, including amitriptyline and serotonin-norepinephrine reuptake inhibitors such as duloxetine, strengthen descending inhibitory pathways by increasing serotonin and noradrenaline levels.

Fornasari also mentioned desvenlafaxine, the active metabolite of venlafaxine, which “has greater activity on descending noradrenergic pathways” and could be particularly useful when the predominant component is noradrenergic.
 

Topical Options

Capsaicin is an option for chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced neuropathy, the expert explained, is related to the overexpression of transient receptor potential cation channel subfamily V member 1, also known as the capsaicin receptor. Topical capsaicin abnormally stimulates these receptors, causing a massive influx of calcium that “defunctionalises the fibre” for periods ranging from a week to 2 months.
 

Clinical Takeaways

Therefore, neuropathic pain, particularly in patients with cancer, requires a multimodal approach that begins with an understanding of the molecular mechanisms to develop personalised treatment options. As Fornasari concluded, “Often, a lack of knowledge of a drug’s mechanism of action leads to its inappropriate, and ultimately ineffective, use.” The challenge for clinicians is to translate this knowledge into tangible improvements for patients, remembering that each patient is unique and requires personalised care that goes beyond standardised protocols.

Clinicians aim to translate these insights into meaningful relief, recognising that each patient requires tailored care.
 

Practical Guidance

• Accurate diagnosis: Screening tools should only be used as support, and decisions should be on the basis of a detailed history and physical examination. In individuals with cancer, the interview always began with the patient’s account.
• Recognising negative prognostic factors: Neuropathic pain, incident pain, psychological distress, delirium, and unrealistic expectations indicate a more difficult course and require a more intensive approach.
• Opioids should be used wisely: Dose escalation should be monitored, rotation should be considered when needed, and psychological factors should be assessed throughout care. As experts have noted, clinicians should try at least 2 or 3 opioids and at least 2 routes of administration before considering invasive procedures.
• Integrating adjuvant medicines early: Gabapentin and other antidepressants are not third-line treatments for individuals with cancer. Adequately dosed for at least 2 weeks to allow therapeutic benefit.
• Consider topical options: In localised peripheral neuropathies, capsaicin can be a valid addition to treatment.
• Use of non-opioid medicines: Some individuals respond exceptionally well to anti-inflammatory agents, with effects that can match those of high morphine doses.

This story was translated from Univadis Italy, part of the this news organization Professional Network.

A version of this article appeared on Medscape.com.

The FDA has approved lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb) for relapsed or refractory marginal zone lymphoma (MZL) in adults after at least two prior lines of systemic therapy.

Lisocabtagene maraleucel (liso–cel) is now the only CD19-directed chimeric antigen receptor (CAR) T–cell therapy approved for MZL. The approval marks liso-cel’s fifth indication, the most of any CD19-directed CAR T–cell therapy, BMS said in a press release. 

Prior approvals are also in the relapsed or refractory setting and include large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma.

MZL is a slow-growing subtype of non-Hodgkin lymphoma (NHL), accounting for about 7% of all NHL cases and typically diagnosed in older adults. Prognosis is generally favorable, but in patients who relapse or become refractory, NHL can transform into diffuse large B-cell lymphoma. 
 

Basis for Approval

Liso-cel’s new approval was based on the MZL cohort of the single arm TRANSFORM FL trial, which included 66 patients in the third or later lines; 95.5% responded to the one-time treatment, with 62.1% having a complete response. Responses were durable in 90.1% of patients at 2 years, according to the BMS press release.

In terms of safety, 76% of MZL patients developed cytokine release syndrome, which was grade 3 or worse in 4.5%. Nervous system disorders included headache (21%, grade ≥ 3 in 1.5%), encephalopathy (21%, grade ≥ 3 in 1.5%), tremor (21%), dizziness (16%), and aphasia (10%). 

Labeling also warns of hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, and secondary malignancies. 
 

Cost of Treatment

One-time treatment costs $567,237.18, according to drugs.com. BMS noted liso-cel is broadly covered by commercial and government insurance programs.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award–winning medical journalist who worked for several major news outlets before joining this news organization. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com

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

The FDA has approved lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb) for relapsed or refractory marginal zone lymphoma (MZL) in adults after at least two prior lines of systemic therapy.

Lisocabtagene maraleucel (liso–cel) is now the only CD19-directed chimeric antigen receptor (CAR) T–cell therapy approved for MZL. The approval marks liso-cel’s fifth indication, the most of any CD19-directed CAR T–cell therapy, BMS said in a press release. 

Prior approvals are also in the relapsed or refractory setting and include large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma.

MZL is a slow-growing subtype of non-Hodgkin lymphoma (NHL), accounting for about 7% of all NHL cases and typically diagnosed in older adults. Prognosis is generally favorable, but in patients who relapse or become refractory, NHL can transform into diffuse large B-cell lymphoma. 
 

Basis for Approval

Liso-cel’s new approval was based on the MZL cohort of the single arm TRANSFORM FL trial, which included 66 patients in the third or later lines; 95.5% responded to the one-time treatment, with 62.1% having a complete response. Responses were durable in 90.1% of patients at 2 years, according to the BMS press release.

In terms of safety, 76% of MZL patients developed cytokine release syndrome, which was grade 3 or worse in 4.5%. Nervous system disorders included headache (21%, grade ≥ 3 in 1.5%), encephalopathy (21%, grade ≥ 3 in 1.5%), tremor (21%), dizziness (16%), and aphasia (10%). 

Labeling also warns of hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, and secondary malignancies. 
 

Cost of Treatment

One-time treatment costs $567,237.18, according to drugs.com. BMS noted liso-cel is broadly covered by commercial and government insurance programs.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award–winning medical journalist who worked for several major news outlets before joining this news organization. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com

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

The FDA has approved lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb) for relapsed or refractory marginal zone lymphoma (MZL) in adults after at least two prior lines of systemic therapy.

Lisocabtagene maraleucel (liso–cel) is now the only CD19-directed chimeric antigen receptor (CAR) T–cell therapy approved for MZL. The approval marks liso-cel’s fifth indication, the most of any CD19-directed CAR T–cell therapy, BMS said in a press release. 

Prior approvals are also in the relapsed or refractory setting and include large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma.

MZL is a slow-growing subtype of non-Hodgkin lymphoma (NHL), accounting for about 7% of all NHL cases and typically diagnosed in older adults. Prognosis is generally favorable, but in patients who relapse or become refractory, NHL can transform into diffuse large B-cell lymphoma. 
 

Basis for Approval

Liso-cel’s new approval was based on the MZL cohort of the single arm TRANSFORM FL trial, which included 66 patients in the third or later lines; 95.5% responded to the one-time treatment, with 62.1% having a complete response. Responses were durable in 90.1% of patients at 2 years, according to the BMS press release.

In terms of safety, 76% of MZL patients developed cytokine release syndrome, which was grade 3 or worse in 4.5%. Nervous system disorders included headache (21%, grade ≥ 3 in 1.5%), encephalopathy (21%, grade ≥ 3 in 1.5%), tremor (21%), dizziness (16%), and aphasia (10%). 

Labeling also warns of hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, and secondary malignancies. 
 

Cost of Treatment

One-time treatment costs $567,237.18, according to drugs.com. BMS noted liso-cel is broadly covered by commercial and government insurance programs.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award–winning medical journalist who worked for several major news outlets before joining this news organization. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com

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

The Medicines and Healthcare products Regulatory Agency (MHRA) has approved tisotumab vedotin (Genmab AS) for adults with recurrent or metastatic cervical cancer.

The decision, made via the International Recognition Procedure, applies to patients whose disease has progressed after prior systemic therapy. It provides a new treatment option for a high-risk group with limited alternatives.

How the Treatment Works

Tisotumab vedotin is an antibody-drug conjugate that combines a tissue factor-directed human monoclonal antibody with monomethyl auristatin E, a microtubule-disrupting agent. The therapy targets tissue factor, which is overexpressed in a several solid tumours, including recurrent cervical cancer.

It is administered as a 30-minute intravenous infusion once every 3 weeks.

What Trials Showed

The approval is based on evidence from multiple clinical studies demonstrating tisotumab vedotin's efficacy in previously treated patients.

In the phase 2 innovaTV 204 study, 102 patients were enrolled and 101 received at least 1 dose of tisotumab vedotin. The confirmed objective response rate was 24%, including seven complete responses and 17 partial responses, demonstrating clinically meaningful activity in a heavily pretreated population.

Further evidence came from the phase 3 innovaTV-301 trial, which randomly assigned 502 patients to receive either tisotumab vedotin or investigator's-choice chemotherapy.

Median overall survival was 11.5 months with the new therapy compared with 9.5 months in the chemotherapy arm, translating to roughly a 30% reduction in the risk for death. The confirmed objective response rate was also significantly higher with tisotumab vedotin—17.8% vs 5.2%—underscoring its advantage over standard treatment options.

Safety and Tolerability

Ocular toxicity and peripheral neuropathy were the most notable adverse reactions.

Common treatment-related events in the phase 2 study included alopecia (38%), epistaxis (30%), nausea, conjunctivitis (26%), and fatigue (26%).

Grade 3 or higher treatment-related adverse events occurred in about 28% of patients. Clinicians should be alert to conjunctivitis and keratitis as well as sensory neuropathic symptoms (numbness, tingling, or a burning sensation in the hands and feet).

Julian Beach, interim executive director of healthcare quality and access at the MHRA, said that patient safety is the agency's "top priority." "We will continue to monitor its safety closely as it becomes more widely used," he added.

The Summary of Product Characteristics and Patient Information Leaflets will be published on the MHRA website within 7 days of approval.

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

The Medicines and Healthcare products Regulatory Agency (MHRA) has approved tisotumab vedotin (Genmab AS) for adults with recurrent or metastatic cervical cancer.

The decision, made via the International Recognition Procedure, applies to patients whose disease has progressed after prior systemic therapy. It provides a new treatment option for a high-risk group with limited alternatives.

How the Treatment Works

Tisotumab vedotin is an antibody-drug conjugate that combines a tissue factor-directed human monoclonal antibody with monomethyl auristatin E, a microtubule-disrupting agent. The therapy targets tissue factor, which is overexpressed in a several solid tumours, including recurrent cervical cancer.

It is administered as a 30-minute intravenous infusion once every 3 weeks.

What Trials Showed

The approval is based on evidence from multiple clinical studies demonstrating tisotumab vedotin's efficacy in previously treated patients.

In the phase 2 innovaTV 204 study, 102 patients were enrolled and 101 received at least 1 dose of tisotumab vedotin. The confirmed objective response rate was 24%, including seven complete responses and 17 partial responses, demonstrating clinically meaningful activity in a heavily pretreated population.

Further evidence came from the phase 3 innovaTV-301 trial, which randomly assigned 502 patients to receive either tisotumab vedotin or investigator's-choice chemotherapy.

Median overall survival was 11.5 months with the new therapy compared with 9.5 months in the chemotherapy arm, translating to roughly a 30% reduction in the risk for death. The confirmed objective response rate was also significantly higher with tisotumab vedotin—17.8% vs 5.2%—underscoring its advantage over standard treatment options.

Safety and Tolerability

Ocular toxicity and peripheral neuropathy were the most notable adverse reactions.

Common treatment-related events in the phase 2 study included alopecia (38%), epistaxis (30%), nausea, conjunctivitis (26%), and fatigue (26%).

Grade 3 or higher treatment-related adverse events occurred in about 28% of patients. Clinicians should be alert to conjunctivitis and keratitis as well as sensory neuropathic symptoms (numbness, tingling, or a burning sensation in the hands and feet).

Julian Beach, interim executive director of healthcare quality and access at the MHRA, said that patient safety is the agency's "top priority." "We will continue to monitor its safety closely as it becomes more widely used," he added.

The Summary of Product Characteristics and Patient Information Leaflets will be published on the MHRA website within 7 days of approval.

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

The Medicines and Healthcare products Regulatory Agency (MHRA) has approved tisotumab vedotin (Genmab AS) for adults with recurrent or metastatic cervical cancer.

The decision, made via the International Recognition Procedure, applies to patients whose disease has progressed after prior systemic therapy. It provides a new treatment option for a high-risk group with limited alternatives.

How the Treatment Works

Tisotumab vedotin is an antibody-drug conjugate that combines a tissue factor-directed human monoclonal antibody with monomethyl auristatin E, a microtubule-disrupting agent. The therapy targets tissue factor, which is overexpressed in a several solid tumours, including recurrent cervical cancer.

It is administered as a 30-minute intravenous infusion once every 3 weeks.

What Trials Showed

The approval is based on evidence from multiple clinical studies demonstrating tisotumab vedotin's efficacy in previously treated patients.

In the phase 2 innovaTV 204 study, 102 patients were enrolled and 101 received at least 1 dose of tisotumab vedotin. The confirmed objective response rate was 24%, including seven complete responses and 17 partial responses, demonstrating clinically meaningful activity in a heavily pretreated population.

Further evidence came from the phase 3 innovaTV-301 trial, which randomly assigned 502 patients to receive either tisotumab vedotin or investigator's-choice chemotherapy.

Median overall survival was 11.5 months with the new therapy compared with 9.5 months in the chemotherapy arm, translating to roughly a 30% reduction in the risk for death. The confirmed objective response rate was also significantly higher with tisotumab vedotin—17.8% vs 5.2%—underscoring its advantage over standard treatment options.

Safety and Tolerability

Ocular toxicity and peripheral neuropathy were the most notable adverse reactions.

Common treatment-related events in the phase 2 study included alopecia (38%), epistaxis (30%), nausea, conjunctivitis (26%), and fatigue (26%).

Grade 3 or higher treatment-related adverse events occurred in about 28% of patients. Clinicians should be alert to conjunctivitis and keratitis as well as sensory neuropathic symptoms (numbness, tingling, or a burning sensation in the hands and feet).

Julian Beach, interim executive director of healthcare quality and access at the MHRA, said that patient safety is the agency's "top priority." "We will continue to monitor its safety closely as it becomes more widely used," he added.

The Summary of Product Characteristics and Patient Information Leaflets will be published on the MHRA website within 7 days of approval.

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