Commentary

Video

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

Heinz-Josef Lenz, MD, FACP, discusses updated data for 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.

Related Videos
Joseph Franses, MD, PhD
Shipra Gandhi, MD
Chih-Yi Liao, MD
Mazyar Shadman, MD, MPH
Sheldon M. Feldman, MD
Rita Mukhtar, MD
Lajos Pusztai, MD, DPhil
Hope S. Rugo, MD
Marc Machaalani, MD
Craig Eckfeldt, MD, PhD, assistant professor, medicine, faculty, Microbiology, Immunology, and Cancer Biology PhD Graduate Program, Division of Hematology, Oncology, and Transplantation, the University of Minnesota Medical School