Overman MJ, et al. - Nivolumab provides clinical benefit in previously treated patients with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC). Herein, the goal was to report the efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC. Treatment with nivolumab + ipilimumab afforded high response rates, encouraging progression-free survival and overall survival [OS] at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. As suggested by indirect comparisons, combination therapy vs anti–programmed death-1 monotherapy offers improved efficacy and has a favorable benefit-risk profile. Nivolumab + ipilimumab affords a promising new treatment option for patients with dMMR/MSI-H mCRC.

• Nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (4 doses) followed by nivolumab 3 mg/kg once every 2 weeks was received by patients.
• Investigator-assessed ORR was the primary end point.

• Among a total of 119 patients, receipt of ≥2 prior systemic therapies was reported in 76%.
• Data revealed that investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80% at median follow-up of 13.4 months.
• Findings also demonstrated that median duration of response was not reached; most responses (94%) were ongoing at data cutoff.
• The reported rates of progression-free survival were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%.
• Patient-reported outcomes, including functioning, symptoms, and quality of life, demonstrated statistically significant and clinically meaningful improvements.
• The occurrence of grade 3 to 4 treatment-related adverse events (AEs) was reported in 32% of patients and these AEs were manageable.
• In addition, an ORR (63%) consistent with that of the overall population was observed in patients (13%) who discontinued treatment because of study drug-related AEs.