Latest news with #metastaticCRC
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.
Medscape
23-06-2025
- Health
- Medscape
Which Second-Line Therapy Is Better for Right-Sided CRC?
TOPLINE: Continuing anti-VEGF therapy plus chemotherapy in the second-line setting led to a small but nonsignificant increase in overall survival in patients with right-sided, RAS/RAF wild-type metastatic colorectal cancer (CRC) compared to patients who received anti-epidermal growth factor receptor (EGFR) therapy plus chemotherapy. METHODOLOGY: Despite limited evidence, guidelines recommend anti-EGFR therapy plus chemotherapy in the second line for patients with RAS/RAF wild-type, right-sided tumors who did not previously receive anti-EGFR therapy. To assess whether this is the best option, the current study compared the effectiveness of continuing chemotherapy plus anti-VEGF in the second-line or using anti-EGFR plus chemotherapy. Researchers used electronic health record data from 280 community oncology clinics in the US. The analysis included 444 patients (median age, 65 years) with RAS/RAF wild-type, right-sided metastatic CRC who received first-line chemotherapy plus anti-VEGF therapy, followed by second-line anti-VEGF therapy (n = 269) or anti-EGFR therapy (n = 175) with chemotherapy. Researchers then compared overall survival in these two groups. TAKEAWAY: Compared with the anti-VEGF therapy group, the anti-EGFR therapy group demonstrated a nonsignificant increased risk for death (hazard ratio [HR], 1.24; P = .10). The median overall survival was 15.3 months with anti-VEGF therapy vs 12.0 months with anti-EGFR therapy. The findings were consistent with first-line trial results, showing nonsignificant worse overall survival with anti-EGFR vs anti-VEGF therapy in right-sided tumors (HR, 1.09). IN PRACTICE: Among patients with RAS/RAF wild-type, right-sided metastatic CRC who received first-line chemotherapy plus anti-VEGF therapy, these findings 'provide some evidence for continuing anti-VEGF therapy in the second line, although the result was not statistically significant,' the authors wrote. SOURCE: This study, led by Nishwant Swami, MD, MPH, Hospital of the University of Pennsylvania, Philadelphia, was published online in JAMA Network Open. LIMITATIONS: This study was limited by possible unmeasured confounding factors and had limited statistical power due to the relatively small proportion of mCRC cases that were right-sided and RAS/RAF wild-type. DISCLOSURES: No funding information was provided for this study. Several authors reported receiving grants and personal fees and having other ties with various sources. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
