Pooled analysis of 2 clinical trials of first-line chemoimmunotherapy for metastatic microsatellite stable colorectal cancer MEDITREME and METIMMOX studies.

چکیده اصلی

BACKGROUND: Colorectal cancer with microsatellite stable (MSS) status is intrinsically resistant to immune checkpoint inhibitor monotherapy targeting PD-1 or PD-L1. However, emerging evidence suggests that chemotherapies may overcome this resistance when combined with immunotherapy. METHODS: We conducted a pooled analysis of individual patient data from two phase II trials evaluating oxaliplatin-based chemotherapy combined with checkpoint inhibitors as first-line treatment for MSS metastatic colorectal cancer. The MEDITREME trial is a single-arm study assessing durvalumab and tremelimumab with oxaliplatin-based chemotherapy, while the METIMMOX trial is a randomized study comparing standard oxaliplatin-based chemotherapy with an alternating regimen of oxaliplatin-based chemotherapy and nivolumab. We compared overall survival (OS), progression-free survival (PFS), and response rates between patients treated with chemotherapy alone versus chemoimmunotherapy, and evaluated the association between these outcomes and transcriptomic and immunoscore data. RESULTS: A total of 130 patients were included: 38 who received chemotherapy alone and 92 chemoimmunotherapy. The median OS was significantly improved in the chemoimmunotherapy group compared with chemotherapy alone (not reached vs. 15.3 months; HR = 0.58; 95% CI, 0.36-0.96; p = 0.03). The complete response rates were higher with chemoimmunotherapy (14% vs. 5%). No significant differences were observed in PFS. High baseline CD8+ T-cell infiltration was associated with improved outcomes in patients receiving chemoimmunotherapy but not in those treated with chemotherapy alone. CONCLUSIONS: This pooled analysis provides compelling evidence supporting the clinical benefit of first-line chemoimmunotherapy in a subset of patients with MSS mCRC. Baseline CD8+ T-cell infiltration may serve as a predictive biomarker for identifying patients most likely to benefit from this treatment approach.

متن کامل اصلی