CheckMate 8HW: Nivolumab Plus Ipilimumab Offers Better PFS for mCRC Over Chemotherapy Alone

At the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Dr. Thierry Andre presented the first results of the CheckMate 8HW study on the use of nivolumab plus ipilimumab versus chemotherapy and nivolumab monotherapy in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).

Standard chemotherapy and targeted therapies often result in poor outcomes for patients with MSI-H/dMMR mCRC, while nivolumab plus ipilimumab has been approved for these patients based on the results of the phase 2 CheckMate 142 study.

The study enrolled a cohort of 303 patients with recurrent or mCRC who were not amenable to surgery. Patients who were previously untreated were randomized 2:2:1 to receive 4 doses of nivolumab (240 mg) plus ipilimumab (1 mg/kg) every 3 weeks followed by nivolumab (480 mg) every 4 weeks, 6 doses of nivolumab (240 mg) every 2 weeks followed by nivolumab (480 mg) every 4 weeks, or chemotherapy with targeted therapy.

Treatment continued until unacceptable toxicity in all arms, or for a maximum of 2 years in the nivolumab plus ipilimumab arm. The primary endpoint for each treatment arm was progression-free survival (PFS). Of 303 patients, 202 were placed in the nivolumab plus ipilimumab arm, and 101 patients were in the chemotherapy arm, while centrally confirmed MSI-H/dMMR was found in 171 and 84 patients in each arm, respectively.

The median follow-up for nivolumab plus ipilimumab was 24.3 months. Nivolumab plus ipilimumab provided meaningful and significant improvement in PFS over chemotherapy alone, and provided a 79% reduction in the risk of disease progression or death (HR 0.21 [95% CI 0.14–0.32]; P<0.0001) along with fewer grade 3 and 4 treatment-related adverse events. First-line nivolumab plus ipilimumab can act as a beneficial standard-of-care option for patients with MSI-H/dMMR mCRC.