Patients with microsatellite instability–high or mismatch repair–deficient colorectal cancer treated with nivolumab plus ipilimumab had a median progression-free survival that was not reached, compared with 5.8 months for patients treated with chemotherapy, according to a recent press release. 

The U.S. Food and Drug Administration (FDA) approved the use of nivolumab (Opdivo, Bristol Myers Squibb) in combination with ipilimumab (Yervoy, Bristol Myers Squibb) for patients aged 12 years and older with unresectable or metastatic microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) colorectal cancer (CRC). The FDA also granted full approval to single-agent nivolumab for the treatment of metastatic MSI-H/dMMR CRC that has progressed after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan, converting its earlier accelerated approval to a standard approval.

Efficacy of the combination was evaluated in CheckMate-8HW (ClinicalTrials.gov identifier NCT04008030), a randomized, three-arm, open-label trial enrolling immunotherapy-naive patients with unresectable or metastatic MSI-H/dMMR CRC. Patients were assigned to receive nivolumab plus ipilimumab, nivolumab monotherapy, or investigator’s choice of chemotherapy. The primary endpoint of the study was progression-free survival (PFS) per blinded independent central review using Response Evaluation Criteria in Solid Tumors version 1.1 in patients with centrally confirmed MSI-H/dMMR status.

In the first-line setting, among 255 patients with centrally confirmed MSI-H/dMMR status, median PFS was not reached in the combination arm (95% confidence interval [CI] = 38.4 months to not estimable) compared with 5.8 months (95% CI = 4.4–7.8 months) in the chemotherapy arm (hazard ratio [HR] = 0.21; 95% CI = 0.14–0.32; P < .0001). In the all-lines analysis, among 582 patients with centrally confirmed status, median PFS was not reached (95% CI = 53.8 months to not estimable) in the combination arm vs 39.3 months (95% CI = 22.1 months to not estimable) with nivolumab monotherapy (HR = 0.62; 95% CI = 0.48–0.81; P = .0003). Objective response rates were 71% (95% CI = 65%–76%) for the combination and 58% (95% CI = 52%–63) for nivolumab monotherapy (P = .0011). Overall survival results were not mature at the time of interim analysis.

Adverse events reported in at least 20% of patients treated with the combination therapy included fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain, and nausea. 

Reference:

U.S. Food and Drug Administration. FDA approves nivolumab with ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer. [press release].