The combination of nivolumab (Opdivo) and low-dose ipilimumab (Yervoy) continues to demonstrate significant and lasting clinical benefits as a first-line treatment for patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (CRC). The latest results from the CheckMate-142 study, presented at the ASCO 2020 virtual annual meeting, reveal a deepening of response and encouraging survival outcomes with extended follow-up.
Heinz-Josef Lenz, MD, FACP, Co-Director of the Gastrointestinal Oncology Program at the University of Southern California Norris Comprehensive Cancer Center, highlighted that this regimen could represent a new first-line therapy option for this patient population, who typically face poor outcomes with standard chemotherapy-based treatments.
Sustained Efficacy and Deepening Responses
The CheckMate-142 study, a multicohort, nonrandomized phase 2 trial, evaluated the combination of nivolumab at 3 mg/kg every 2 weeks and ipilimumab at 1 mg/kg every 6 weeks. With a median follow-up of 29 months, the median duration of response, progression-free survival (PFS), and overall survival (OS) had not yet been reached. This indicates a sustained and durable response to the treatment.
An earlier analysis with a median follow-up of 13.8 months had already suggested durable clinical benefits. The latest data reinforce these findings, showing that 84% of patients experienced a reduction in tumor burden from baseline. At 24 months, the PFS rate was 74%, and the OS rate was 79%.
Patient Characteristics and Treatment Outcomes
The study included 45 patients, with 38% having metastatic CRC with BRAF mutation, 22% with KRAS mutations, and 18% with Lynch syndrome. At the data cutoff, 33% of patients were still receiving treatment. Disease progression was the most common reason for treatment discontinuation (18%), while 13% discontinued due to maximal clinical benefit, and another 13% due to treatment-related adverse events.
The investigator-assessed objective response rate (ORR) increased from 60% at 13.8 months to 69% at the 29-month follow-up. The complete response (CR) rate also improved, rising from 7% to 13%, with three additional patients achieving a complete response and one achieving a partial response since the previous data cutoff in July 2018. The disease control rate (DCR) was 84% at the latest follow-up.
Treatment-Free Interval and Subsequent Therapies
Of the 45 patients, 15 (33%) continued on the study treatment, 11 discontinued and received subsequent therapies, and 19 were treatment-free. Among the 19 patients who stopped treatment, 14 had at least one tumor assessment during the treatment-free interval, including two with a complete response, seven with a partial response, and one with stable disease.
Safety Profile
The safety profile of nivolumab plus low-dose ipilimumab remained consistent with longer follow-up, and no new safety signals were identified. The combination was well-tolerated, with 22% of patients experiencing grade 3 or 4 treatment-related adverse events, and only 7% discontinuing treatment due to these adverse events, according to Dr. Lenz.
