Comparative efficacy and safety of nivolumab-based combination therapies (with ipilimumab or binimetinib) in patients with microsatellite-stable and microsatellite-instability-high metastatic colorectal cancer: a systematic review and meta-analysis.

In 30 seconds

This systematic review and meta-analysis pooled three randomized controlled trials involving 1085 patients with metastatic colorectal cancer to compare nivolumab-based combinations, including ipilimumab- or binimetinib-containing regimens, with control regimens. Overall best response did not differ significantly between groups (RR 1.01; 95% CI 0.79-1.30; p = 0.94). Partial response rates improved with combination therapy, while complete response, stable disease and progressive disease rates were unchanged. Treatment-related adverse events were numerically more frequent but not significantly so (RR 1.19; 95% CI 0.86-1.65; p = 0.30).

Key findings

• Overall best response was similar with nivolumab-based combinations and controls (RR 1.01; 95% CI 0.79-1.30; p = 0.94; I 2 = 56%).
• Partial response rates were significantly higher with combination therapy; complete response, stable disease and progressive disease rates were unchanged.
• Treatment-related adverse events showed a non-significant numerical increase (RR 1.19; 95% CI 0.86-1.65; p = 0.30).

Why it matters

The findings distinguish an increase in partial responses from improvement in overall best response, and indicate that the pooled trials did not establish a significant overall response advantage. The safety estimate also does not show a statistically significant increase in treatment-related adverse events. These results underscore the importance of selecting patients likely to benefit, particularly given the differing immunotherapy effectiveness described for MSI-H and MSS disease.

What to keep in mind

The meta-analysis included only three trials, and overall response estimates had moderate heterogeneity (I 2 = 56%).