Nivolumab and ipilimumab

In a single-arm cohort of the phase II, multicenter CheckMate-142 study (NCT02060188) presented in abstract form, 45 treatment-naïve patients with MSI-H/dMMR metastatic colorectal cancer received nivolumab (3 mg/kg every 2 weeks) with ipilimumab (1 mg/kg every 6 weeks). The primary end point was objective response rate.[70]

In a single-arm cohort of the phase II, multicenter CheckMate-142 study (NCT02060188) presented in abstract form, 45 treatment-naïve patients with MSI-H/dMMR metastatic colorectal cancer received nivolumab (3 mg/kg every 2 weeks) with ipilimumab (1 mg/kg every 6 weeks). The primary end point was objective response rate.[70]

The objective response rate was 69% among all enrolled patients and 80% for patients with KRAS variants (n = 10).[70][Level of evidence C2]

In a single-arm cohort of the phase II, multicenter CheckMate-142 study (NCT02060188) presented in abstract form, 45 treatment-naïve patients with MSI-H/dMMR metastatic colorectal cancer received nivolumab (3 mg/kg every 2 weeks) with ipilimumab (1 mg/kg every 6 weeks). The primary end point was objective response rate.[70]

At a 2-year clinical follow-up, the median PFS and OS had not been reached.

In the CheckMate 8HW trial (NCT04008030), published in abstract form, 303 patients who had received various lines of treatment were randomly assigned to receive either nivolumab and ipilimumab (n = 202) or chemotherapy alone (n = 101). Some patients were also randomly assigned to receive nivolumab, but results from these patients were not presented in the abstract. Treatments were continued until progression or unacceptable toxicity (all arms), or for up to 2 years (nivolumab-ipilimumab arm). A total of 171 patients who received nivolumab and ipilimumab and 84 patients who received chemotherapy alone were centrally confirmed to have dMMR/MSI-H metastatic colorectal cancer.[71]

In the CheckMate 8HW trial (NCT04008030), published in abstract form, 303 patients who had received various lines of treatment were randomly assigned to receive either nivolumab and ipilimumab (n = 202) or chemotherapy alone (n = 101). Some patients were also randomly assigned to receive nivolumab, but results from these patients were not presented in the abstract. Treatments were continued until progression or unacceptable toxicity (all arms), or for up to 2 years (nivolumab-ipilimumab arm). A total of 171 patients who received nivolumab and ipilimumab and 84 patients who received chemotherapy alone were centrally confirmed to have dMMR/MSI-H metastatic colorectal cancer.[71]

At a median follow-up of 31.5 months, the PFS was superior for patients who received nivolumab and ipilimumab compared with those who received chemotherapy alone (HR, 0.21; 97.91% CI, 0.13–0.35; P < .0001). Of note, in the chemotherapy arm, 67% of patients received subsequent immunotherapy.

In the CheckMate 8HW trial (NCT04008030), published in abstract form, 303 patients who had received various lines of treatment were randomly assigned to receive either nivolumab and ipilimumab (n = 202) or chemotherapy alone (n = 101). Some patients were also randomly assigned to receive nivolumab, but results from these patients were not presented in the abstract. Treatments were continued until progression or unacceptable toxicity (all arms), or for up to 2 years (nivolumab-ipilimumab arm). A total of 171 patients who received nivolumab and ipilimumab and 84 patients who received chemotherapy alone were centrally confirmed to have dMMR/MSI-H metastatic colorectal cancer.[71]

Two grade 5 deaths occurred in the nivolumab-ipilimumab arm. Grade 3 to 4 events occurred in 23% of patients in the nivolumab-ipilimumab arm and 48% of patients in the chemotherapy-alone arm.