Nivolumab Plus Ipilimumab Offers Improved Survival Outcomes in Certain Metastatic CRC Patients

The combination of nivolumab and ipilimumab yielded high response rates and encouraging survival outcomes in a cohort of previously treated patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC).

“Patients with dMMR/MSI-H mCRC (approximately 4% of patients) are a distinct biomarker-defined population that benefits less from conventional chemotherapy,” wrote study authors led by Michael J. Overman, MD, of the University of Texas MD Anderson Cancer Center in Houston. Previously reported results from the CheckMate-142 trial showed that nivolumab monotherapy resulted in a response rate in this patient setting of 31%, and a 12-month overall survival rate of 73%.

The new analysis included 119 patients from another CheckMate-142 cohort who received nivolumab along with ipilimumab; the combination is already approved for use in metastatic melanoma. In this cohort, 76% of patients had received at least two prior systemic therapies, and they were followed for a median of 13.4 months. Results were published online ahead of print on January 20 in the Journal of Clinical Oncology.

A total of 65 patients (54.6%) achieved an objective response, including four complete responses (3.4%) and 61 partial responses (51.3%). Disease control for at least 12 weeks was achieved in 80% of patients, and 12% of patients had progressive disease as their best response. The median time to response was 2.8 months, and responses were durable; 94% had an ongoing response at the time of data cutoff. The median duration of response was not reached, and 83% had responses that lasted at least 6 months. Median progression-free survival (PFS) was not reached, and the 12-month PFS rate was 71%. Median overall survival (OS) was also not yet reached, with a 12-month OS rate of 85%.

The study also included patient-reported outcome (PRO) questionnaires. While on study, at least 60% of patients maintained functioning and global health status/quality of life (QOL) without worsening of symptoms based on the European Organisation for Research and Treatment of Cancer quality of life questionnaire C30 (EORTC QLQ-C30). Significant and clinically meaningful improvements from baseline were seen with regard to symptoms, functioning, and global health status/QOL by week 13 or earlier.

Treatment-related adverse events (TRAEs) were reported in 73% of patients, with 27% experiencing grade 3 TRAEs and 5% experiencing grade 4 TRAEs. The most common grade 3/4 TRAEs included elevated AST and/or ALT, elevated lipase, anemia, and colitis. TRAEs led to discontinuation of therapy in 13% of patients.

“The results presented here demonstrate that nivolumab in combination with ipilimumab provided durable responses, high disease control rate, encouraging survival rates, manageable safety, and meaningful improvements in key PROs in previously treated patients with dMMR/MSI-H mCRC,” the authors concluded, calling the combination a “promising new treatment option” in this setting. A phase II trial of the combination as a first-line therapy is underway.