First-line treatment with nivolumab and ipilimumab produced lasting responses in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC), according to results published in the Journal of Clinical Oncology.
Researchers tested this combination in the phase 2 CheckMate 142 trial (ClinicalTrials.gov Identifier: NCT02060188). The trial included 45 patients with MSI-H/dMMR mCRC who had not received prior therapy for metastatic disease.
The patients’ median age was 66 years (range, 21-84 years), 51% were men, 38% had BRAF mutations, and 22% had KRAS mutations.
The patients received a median of 34 (range, 1-68) doses of nivolumab (3 mg/kg once every 2 weeks) and 12 (range, 1-23) doses of ipilimumab (1 mg/kg once every 6 weeks).
The median follow-up was 29.0 months. According to investigator assessment, the objective response rate (ORR) was 69%. This included 6 complete and 25 partial responses. The ORR was 76% in patients with a BRAF mutation, 80% in those with a KRAS mutation, and 62% for patients with wild-type BRAF and KRAS.
The median duration of response, median progression-free survival (PFS), and median overall survival (OS) were not reached. The 12-month OS rate was 84.1%, and the 24-month OS rate was 79.4%.
In the overall population, the 12-month PFS rate was 76.4%, and the 24-month PFS rate was 73.6%. The 24-month PFS rate was 87.5% for patients with KRAS mutations, 76.5% for those with BRAF mutations, and 68.4% for patients with wild-type BRAF and KRAS.
Of the 14 evaluable patients who discontinued treatment and did not receive subsequent therapy, 10 were progression-free at last follow-up.
Treatment-related adverse events (TRAEs) were observed in 80% of patients. The most common of these events were pruritus (36%), arthralgia (20%), and hypothyroidism (18%).
Grade 3-4 TRAEs occurred in 22% of patients, and serious TRAEs occurred in 16%. TRAEs led to treatment discontinuation in 13% of patients.
Based on these results, the researchers concluded that “nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated.”
In a confirmatory phase 3 study (ClinicalTrials.gov Identifier: NCT04008030), researchers are comparing nivolumab plus ipilimumab with chemotherapy or nivolumab monotherapy in this patient population.
Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Lenz HJ, Van Cutsem E, Limon ML, et al. First-line nivolumab plus low-dose ipilimumab for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: The phase II CheckMate 142 study. J Clin Oncol. Published online October 12, 2021. doi:10.1200/JCO.21.01015