Combination Immunotherapy in DNA Mismatch Repair–Deficient/Microsatellite Instability–High Metastatic Colorectal Cancer


Key Points

  • Nivolumab plus ipilimumab produced response in 55% of patients.
  • At median follow-up of 13 months, median duration of response was not reached. 

As reported in the Journal of Clinical Oncology by Overman et al, findings in the nivolumab (Opdivo) plus ipilimumab (Yervoy) cohort of the CheckMate-142 study indicate a high response rate and durable responses with the combination in previously treated patients with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer. Data from the nivolumab monotherapy cohort in CheckMate-142 supported the approval of nivolumab in this setting. 

Study Details

In the study, 119 patients were enrolled between May 2015 and September 2016 and treated with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks for four doses followed by nivolumab 3 mg/kg every 2 weeks. Overall, 76% of patients had received ≥ 2 prior systemic therapies. The primary endpoint was investigator-assessed objective response rate.

Response Rates

Median follow-up was 13.4 months; 75 patients (63%) were still receiving treatment at data cutoff. Objective response was observed in 65 patients (55%), including complete response in four. The rate of disease control for ≥ 12 weeks was 80%. Median duration of response was not reached, with most responses (94%) being ongoing at data cutoff. Progression-free survival was 76% at 9 months and 71% at 12 months. Overall survival was 87% at 9 months and 85% at 12 months.

Adverse Events

Grade 3 or 4 treatment-related adverse events occurred in 32% of patients, with the most common being increased AST (8%) and increased ALT (8%). Among the 13% of patients who discontinued treatment due to treatment-related adverse events, the objective response rate (63%) was similar to that in the total population.

Statistically significant and clinically meaningful improvements from baseline were observed on the EORTC Core Quality of Life Questionnaire (QLQ-C30) for symptoms, functioning, and global health status/QOL.

The investigators concluded, “Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and [overall survival] at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti–programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H [metastatic colorectal cancer].”

The study was supported by Bristol-Myers Squibb.

Michael J. Overman, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.