The first-line immunotherapy combination of nivolumab (Opdivo) and low-dose ipilimumab (Yervoy) continues to show robust, durable clinical benefit, with a deepening of response, in patients with microsatellite instability high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (CRC), according to results presented at the ASCO 2020 virtual annual meeting.
In the CheckMate-142 study, at a median follow-up of 29 months, the median duration of response, median progression-free survival (PFS), and median overall survival (OS) had not yet been reached with the immunotherapy doublet, reported lead investigator Heinz-Josef Lenz, MD, FACP, Co-Director, Gastrointestinal Oncology Program, University of Southern California Norris Comprehensive Cancer Center, Los Angeles.
As such, “nivolumab and low-dose ipilimumab may represent a new first-line therapy option for patients with MSI-high and mismatch repair-deficient metastatic colorectal cancer,” said Dr Lenz.
Patients with MSI-H or dMMR metastatic CRC who receive first-line chemotherapy-based regimens have poor outcomes, representing an unmet need, according to Dr Lenz. The combination of nivolumab and ipilimumab already showed efficacy in previously treated patients with MSI-H or dMMR metastatic CRC from the CheckMate-142 trial. Based on these results, nivolumab as a single agent or in combination with ipilimumab received accelerated approval from the FDA for patients whose disease progressed after treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
An earlier analysis (median follow-up, 13.8 months) of outcomes from the CheckMate-142 study using this combination in the first-line setting in patients with MSI-H or dMMR CRC showed durable clinical benefit.
CheckMate-142 is an ongoing, multicohort nonrandomized phase 2 study. In the single-arm study, patients received treatment with nivolumab 3 mg/kg every 2 weeks, plus ipilimumab 1 mg/kg every 6 weeks, until disease progression or discontinuation.
Between the previous analysis at 13.8 months of follow-up and the current analysis at a median follow-up of 29 months, “the majority of patients experienced a deepening of response,” Dr Lenz noted. In all, 84% of patients had a reduction in tumor burden from baseline. At 24 months, the median PFS rate was 74% and the median OS rate was 79%.
The study population consisted of 45 patients, 38% of whom had metastatic CRC with BRAF mutation, 22% had KRAS mutations, and 18% had Lynch syndrome. At data cutoff, 33% of the patients were still receiving treatment.
The most common reason for treatment discontinuation was disease progression in 18% of patients, 13% had achieved maximal clinical benefit, and 13% discontinued treatment because of an adverse event related to the treatment regimen.
At the latest follow-up, the investigator-assessed objective response rate was 69%, an increase from 60% at the median 13.8-month follow-up. The complete response rate at the 29-month median follow-up was 13% (vs 7% at 13.8 months), including 3 additional patients with a complete response and 1 additional patient with a partial response since the July 2018 cutoff. The disease control rate was 84% at the latest follow-up.
Of the 45 patients, 15 (33%) continued to use the study treatment, 11 stopped the study treatment and received subsequent therapies, and 19 were treatment-free. Of the 19 patients who stopped treatment, 14 had at least 1 tumor assessment during the treatment-free interval, including 2 patients with a complete response, 7 with a partial response, and 1 with stable disease.
The safety profile of nivolumab plus low-dose ipilimumab remained similar with longer follow-up, and no new safety signals were reported at the latest follow-up. The doublet immunotherapy regimen remained well-tolerated, with 22% of patients having grade 3 or 4 treatment-related adverse events, and only 7% of patients discontinuing treatment because of grade 3 or 4 treatment-related adverse events, said Dr Lenz.