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

<h4>Background</h4>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.<h4>Methods</h4>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 <i>versus</i> chemoimmunotherapy, and evaluated the association between these outcomes and transcriptomic and immunoscore data.<h4>Results</h4>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 <i>vs</i>. 15.3 months; HR = 0.58; 95% CI, 0.36-0.96; <i>p</i> = 0.03). The complete response rates were higher with chemoimmunotherapy (14% <i>vs</i>. 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.<h4>Conclusions</h4>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.