Latest news with #dMMR
Medscape
18-07-2025
- Health
- Medscape
Early ctDNA Changes Predict Immunotherapy Outcomes in CRC
TOPLINE: In patients with deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (CRC) who received immune checkpoint inhibitors, changes in circulating tumor DNA (ctDNA) concentrations at 1-month post-treatment predicted progression-free survival (PFS) and overall survival. Favorable ctDNA responders experienced significantly improved survival with the immune checkpoint inhibitor avelumab than with chemotherapy. METHODOLOGY: Immune checkpoint inhibitors have improved outcomes among patients with dMMR/MSI-H metastatic CRC, but early resistance is common, and the optimal treatment duration remains unclear. Using liquid biopsy to monitor ctDNA changes may enable earlier prediction of long-term outcomes, but this approach requires further validation. Researchers performed a secondary analysis using data from the SAMCO-PRODIGE 54 trial, in which 99 patients with dMMR/MSI-H metastatic CRC (mean age, 66 years; 51.5% women) were randomly assigned to receive either avelumab every 15 days or standard chemotherapy with or without targeted therapy. Researchers collected plasma samples at baseline and 1 month after treatment initiation and analyzed ctDNA using digital droplet polymerase chain reaction assays. Favorable ctDNA responders were defined as those who exhibited a decline in ctDNA concentrations greater than or equal to the median value (-86%), whereas poor responders were those with a decline less than the median value. Researchers assessed PFS and overall survival according to baseline ctDNA positivity or concentration as well as early ctDNA variation. TAKEAWAY: Changes in ctDNA concentration were significantly associated with both PFS (hazard ratio [HR], 2.98; P < .001) and overall survival (HR, 3.61; P < .001). This association was stronger in the avelumab group (HR, 4.22 for PFS and HR, 17.44 for overall survival) vs the chemotherapy group (HR, 2.09 and HR, 1.51; P = .38, respectively). In the avelumab group, the median PFS was 29.0 months for favorable ctDNA responders vs 2.3 months for poor responders; median overall survival was not reached among favorable responders compared with 15.0 months among poor responders (HR, 17.40; P < .001). Compared with chemotherapy, avelumab was associated with significantly improved PFS for favorable ctDNA responders (HR, 0.33) but not for poor responders (HR, 1.32). In multivariable analysis, a change in ctDNA concentration was confirmed to be independently associated with PFS in patients treated with avelumab (HR, 7.27; P = .001) but not in those treated with chemotherapy. Several patients with a poor ctDNA response did have long-lasting stable disease — indicating that cDNA change is 'informative,' the authors noted, but not in itself enough to drive decisions on early treatment discontinuation. IN PRACTICE: 'Our findings suggest that change in ctDNA may theoretically be useful for early prediction of immune checkpoint inhibitor efficacy,' the author concluded. 'Therefore, the added value of change in ctDNA is having an earlier assessment and providing additional information on the long-term outcome of the disease compared with a classic RECIST assessment.' SOURCE: The study, led by Julien Taïeb, MD, PhD, Service de gastroenterologie et d'oncologie digestive, Paris CARPEM institute, Hopital Européen Georges Pompidou, Assistance Publique Hopitaux de Paris, Université Paris Cité in Paris, France, was published online in JAMA Oncology. LIMITATIONS: The study was limited by a moderate sample size, particularly affecting the interpretation of subgroup analyses. A potential risk for immortal-time bias could have been introduced as the study endpoints were defined from randomization to the event, but patients were not at risk until at least 4 weeks post-treatment. Additionally, having only a single ctDNA monitoring timepoint may have affected outcome predictions. DISCLOSURES: The SAMCO-PRODIGE 54 phase 2 randomized clinical trial received partial funding from Merck KGAa and was sponsored by the Fédération Francophone de Cancérologie digestive. Several authors reported receiving grants or personal fees and having other ties with various sources. 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.
Medical News Today
05-06-2025
- Health
- Medical News Today
Colon cancer: Adding immunotherapy may halve death, recurrence rate
Combining immunotherapy nd chemotherapy may give better results for treating colon cancer, research shows. wilpunt/Getty Images While there are several treatment options for colon cancer, not all of them work for all cancer types. Deficient mismatch repair (dMMR) colon cancer is known to be less responsive to chemotherapy than other types. A new study reports that adding immunotherapy to chemotherapy after surgery for stage 3 colon cancer may help decrease a person's recurrence and death rate by half. However, not all treatments work for all types of colorectal cancer. For example, deficient mismatch repair (dMMR) colon cancer , which is caused by mutations in genes that correct mistakes that happen when a person's DNA is copied, encompasses 5-15% of colorectal cancer cases and may not be as responsive to chemotherapy as other types. Now, a new study presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting reports that adding immunotherapy to chemotherapy after surgery for stage 3 colon cancer may help decrease a person's recurrence and death rate by half. The findings are yet to be published in a peer-reviewed journal. For this phase III clinical trial, researchers recruited 712 people with an average age of 64 who had dMMR stage 3 colon cancer. This stage of colorectal cancer occurs when the cancer spreads to the body's lymph nodes, but nowhere else. All study participants had undergone surgery to have their cancer removed and still had cancer cells in their lymph nodes. Atezolizumab targets a specific protein in cancer cells called programmed death-ligand 1 (PD-L1) . PD-L1's job is to keep cancer cells 'hidden' from detection by the body's immune system. By binding and blocking to PD-L1, atezolizumab makes the cancer cells 'visible' to the immune system so it can attack them. At the study's conclusion, researchers found that participants receiving chemotherapy with immunotherapy had a 50% decrease in cancer recurrence and death — known as disease-free survival (DFS) — compared to those who only received chemotherapy. 'The findings from our study represent a major advance in the adjuvant treatment of dMMR stage 3 colon cancer and will now change the treatment for this type of cancer,' says Frank Sinicrope, MD, oncologist at the Mayo Clinic in Minnesota and lead author of this study, in a press release. 'It's extremely rewarding to be able to offer our patients a new treatment regimen that can reduce the risk of recurrence and improve their chances of survival,' he says. 'We're changing the paradigm in colon cancer treatment. By using immunotherapy at earlier stages of disease, we are achieving meaningful benefits for our patients.' — Frank Sinicrope, MD Medical News Today spoke with Glenn S. Parker, MD, FACS, FASCRS, vice chairman of surgery and chief of colorectal surgery at Hackensack Meridian Jersey Shore University Medical Center in New Jersey, about this study who commented that his first reaction to these findings was a strong sense of hope. 'The use of atezolizumab, an immune checkpoint inhibitor, alongside standard chemotherapy in stage III dMMR colon cancer represents a significant step forward in the care of our patients,' Parker explained. 'Patients with dMMR colon cancer often have a distinct tumor biology that affects how they respond to chemotherapy. Although they generally have a better prognosis, recurrence still occurs, and current treatments may not be optimal for this group.' 'Developing therapies that work with the immune system, like atezolizumab, could specifically target the molecular genetics of dMMR tumors and significantly reduce the chance of cancer returning, leading to better long-term outcomes.' — Glenn S. Parker, MD, FACS, FASCRS Parker said he would like to see extended follow-up from the clinical trial to evaluate long-term survival and recurrence data. 'Additionally, further studies should explore whether immunotherapy could eventually reduce the length of time for both adjuvant chemotherapy/immunotherapy in some dMMR patients, particularly those with high immune activation profiles,' he continued. 'Biomarker analyses and quality-of-life assessments will also be critical in determining which patients benefit the most from combined therapy and how best to integrate this approach into standard of care,' he added. MNT also spoke with Wael Harb, MD, a board certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in Orange County, CA, about this research, who said he was genuinely excited by the trial's results. 'Colon cancer is one of the most common and deadly cancers worldwide,' he continued. 'Even after surgery, many patients — especially those with stage III disease — face a real risk that their cancer will return. For people with dMMR tumors, traditional chemotherapy doesn't always offer enough protection. What makes this group unique is that their tumors are especially responsive to immunotherapy. So finding new ways — like this study — to harness the immune system gives us a much better shot at keeping the cancer from coming back,' Harb explained. 'This study is a major step forward for patients with stage III colon cancer who have a specific genetic feature called dMMR. The combination of standard chemotherapy with the immunotherapy drug atezolizumab cut the risk of cancer recurrence and death by 50%. That's a dramatic improvement — and in the world of cancer care, results like these can lead to real changes in how we treat patients. It's the kind of data that could redefine the standard of care.' — Wael Harb, MD Harb said the most important next step for this research is to see this approach integrated into treatment guidelines, so doctors everywhere can offer it to eligible patients. 'I'd also like to see longer-term follow-up data to confirm the durability of benefit and monitor safety over time. And looking ahead, it would be exciting to explore whether immunotherapy could also help patients with earlier-stage disease — or even be used instead of chemotherapy in some cases. Ultimately, this study opens the door to more personalized and effective treatments for colon cancer,' he added. Colorectal Cancer Cancer / Oncology Immune System / Vaccines
