Dr Lenz on Frontline Nivolumab Plus Ipilimumab in MSI-H/dMMR mCRC

Heinz-Josef Lenz, MD, FACP, associate director, Clinical Research, chair, Gastrointestinal Oncology Program, codirector, Colorectal Center, University of Southern California Norris Comprehensive Cancer Center; professor, Department of Medicine, Department of Preventive Medicine, Division of Oncology, Keck School of Medicine, discusses findings from an expanded efficacy analysis from the phase 3 CheckMate 8HW trial (NCT04008030).

CheckMate 8HW evaluated frontline nivolumab (Opdivo) plus ipilimumab (Yervoy) vs chemotherapy in patients with previously untreated, microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) metastatic colorectal cancer (mCRC).

At the 2024 ASCO Annual Meeting, Lenz and colleagues presented further data from this randomized phase 3 study, which enrolled patients with unresectable or metastatic CRC with MSI-H/dMMR status confirmed by local testing. Participants were randomly assigned in a 2:2:1 fashion to receive nivolumab at 240 mg plus ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab at 480 mg every 4 weeks; the same regimen of nivolumab as a single agent; or chemotherapy with or without targeted therapies. Treatment continued until disease progression or unacceptable toxicity, or for up to two years in the nivolumab arms.

The primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) assessment per RECIST 1.1 criteria for nivolumab plus ipilimumab vs chemotherapy in the first-line setting, and the combination vs nivolumab alone in all therapy lines.

Findings showed that at a median follow-up of 31.5 months, treatment with nivolumab plus ipilimumab in the frontline setting led to a 79% reduction in the risk of disease progression or death compared with chemotherapy (HR, 0.21; 97.91% CI, 0.13-0.35; P < .0001). The median PFS was not reached (NR; 95% CI, 38.4-NR) in the combination arm vs 5.9 months (95% CI, 4.4-7.8) in the chemotherapy arm.

Additionally, time to second progression (PFS2) was extended in the frontline combination arm vs the chemotherapy arm (HR, 0.27; 95% CI, 0.17-0.44). The median PFS2 was NR (95% CI, NR-NR) in the combination arm vs 29.9 months (95% CI, 14.8-NR) in the chemotherapy arm.