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

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.