Dr Morris on the Clinical Benefit With Nivolumab Plus Ipilimumab Across dMMR/MSI-H mCRC Subgroups

"Even though the [CheckMate 8HW] trial wasn’t powered to compare various subpopulations of CRC, between the nivolumab/ipilimumab vs nivolumab [monotherapy] arms, there was consistent benefit observed across [subgroups with the combination]. This gives us confidence to use dual immune checkpoint blockade as an FDA-approved option for patients with untreated MSI-H mCRC."

Van Karlyle Morris, MD, an associate professor in the Department of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed the consistent benefit observed with nivolumab (Opdivo) plus ipilimumab (Yervoy) across subgroups of adult and pediatric patients at least 12 years of age with mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) unresectable or metastatic colorectal cancer (CRC).

On April 8, 2025, the FDA approved the combination of nivolumab and ipilimumab for this patient population based on findings from the phase 3 CheckMate 8HW trial (NCT04008030), which demonstrated a progression-free survival (PFS) advantage for the combination over nivolumab alone (HR, 0.62; 95% CI, 0.48-0.81; P = .0003), Morris stated.

The 2-year PFS rates favored the combination, at 71% compared with 56% with nivolumab monotherapy, Morris noted. Similarly, the overall response rate was higher with dual checkpoint blockade, at 71% (95% CI, 65%-76%) vs 58% (95% CI, 52%-63%) with nivolumab monotherapy (P = .0011), Morris added.

Although the trial was not powered to detect differences across molecular or clinical subgroups, consistent benefit with the combination was observed across multiple stratification factors used in metastatic CRC, Morris stated. Additionally, the efficacy of the combination was maintained regardless of primary tumor sidedness, with similar outcomes observed in patients with left- vs right-sided primary tumors, Morris explained. Additionally, sites of metastatic disease—such as liver and peritoneal metastases—demonstrated trends favoring dual checkpoint inhibition, Morris said.

Importantly, the benefit of the combination also extended to patients with BRAF V600E mutations, which are generally associated with poorer prognosis in metastatic CRC, Morris commented. These results support the use of nivolumab plus ipilimumab as a frontline immunotherapy option in patients with untreated MSI-H or dMMR mCRC, Morris concluded.