OBJECTIVES: This study compared overall survival (OS) in patients receiving nivolumab + low-dose ipilimumab in CheckMate 142 versus patients in the real world (RW) receiving standard of care (SOC) therapy for second-line and later (2L+) microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC). CheckMate 142 is an ongoing, multi-cohort, nonrandomized phase 2 trial, and these results contextualize survival outcomes for Cohort 2 nivolumab + low-dose ipilimumab versus SOC.

METHODS: The RW SOC cohort was constructed using Flatiron Health oncology electronic health record data from January 2013 through January 2021. The nivolumab + low-dose ipilimumab cohort used 4-year follow-up data from CheckMate 142 (data cutoff October 2020). The primary patient-level analysis was performed using doubly robust inverse probability of treatment weighting (IPTW) with subsequent time-to-event modeling for OS.

RESULTS: Following IPTW, the distributions of the following potential confounders were balanced, with standardized mean differences (SMDs) within the 0.20 threshold: sex, BRAF mutational status, Eastern Cooperative Oncology Group baseline scores, and primary tumor location. SMDs were reduced for all other included covariates, but differences above the 0.20 threshold remained for: age (SMD = −0.29), race (SMD = 0.37), disease stage at initial diagnosis (SMD = 0.27), number of lines of prior therapy (SMD = 0.80), type of prior therapy (SMD = 0.97), and KRAS mutational status (SMD = 0.21). Median OS was not reached (95% CI, not reached) in patients receiving nivolumab + low-dose ipilimumab versus 20.0 months (95% CI, 7.5–32.6) in patients receiving SOC, with a hazard ratio of 0.36 (95% CI, 0.17–0.80). Multiple sensitivity analyses, including a matched analysis, confirmed the robustness of the primary analysis.

CONCLUSIONS: This study provides supportive evidence for the effectiveness of nivolumab + low-dose ipilimumab for patients with MSI-H/dMMR mCRC in the 2L+ setting relative to SOC.