Combining nivolumab with ipilimumab demonstrated clinical benefit and a manageable safety profile among patients with DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer, according to results of a study scheduled for presentation at the Gastrointestinal Cancers Symposium.
“In this nonrandomized study, nivolumab [Opdivo, Bristol-Myers Squibb] plus ipilimumab [Yervoy, Bristol-Myers Squibb) provided improved clinical benefit relative to nivolumab monotherapy, with manageable safety,” Thierry Andre, MD, professor of medical oncology at Saint-Antoine Hospital in Paris, told HemOnc Today. “Nivolumab plus ipilimumab is a new treatment option in previously treated patients with DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. These results are real hope for patients, with high and durable response rates and high disease control rates.”
Results of the CheckMate 142 trial showed that nivolumab conferred a 31% overall response rate and a 69% disease control rate among pretreated patients with DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer.
An interim analysis of CheckMate 142 showed the combination cohort of nivolumab plus ipilimumab yielded a preliminary ORR of 55% and a manageable safety profile in a subset of 84 patients with more than 6 months of follow-up.
Andre and colleagues evaluated the efficacy and safety of nivolumab and ipilimumab in the complete combination cohort (n = 119) of CheckMate 142, which is the largest single-study report of an immunotherapy regimen among patients with DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer.
Patients received 3 mg/kg nivolumab plus 1 mg/kg ipilimumab every 3 weeks for four doses, followed by 3 mg/kg nivolumab monotherapy every 2 weeks.
ORR served as the primary endpoint. Secondary endpoints included duration of response, PFS, OS and safety/tolerability.
Median follow-up was 13.4 months.
Seventy-six percent of patients had more than two prior lines of therapy.
Researcher reported an ORR of 55% (95% CI, 45.2-63.8) — which did not change for patients with a BRAF mutation — and disease control rate of 80% (95% CI, 71.5-86.6). Three percent of patients achieved a complete response, 51% achieved a partial response and 31% showed stable disease.
Among all responders, the duration of response was not reached because 94% of responses remained ongoing at data cutoff.
Seventy-seven percent of patients showed a reduction in tumor burden from baseline.
Seventy-six percent of patients achieved 9-month PFS and 87% achieved 9-month OS.
Grade 3 or grade 4 treatment-related adverse events occurred among 32% of patients. Additionally, 13% of patients with adverse events of any grade and 10% of those with grade 3 or grade 4 adverse events discontinued treatment. No treatment-related deaths occurred.
“Because the rate of cure in cases of metastatic disease is low, we hope that with these data it will be possible to obtain labeling in the United States and in Europe,” Andre said. “In Europe, no labeling exists for immunotherapy for DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer and it is important to get this therapy to patients.” – by Chuck Gormley
Disclosures: Bristol-Myers Squibb funded the study. Andre reports consultant/advisory roles with Amgen, Bristol-Myers Squibb, HalioDX, MSD Oncology, Mundipharma, Roche/Genentech and Servier, as well as honoraria from Baxter, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, MSD Oncology, Novartis, Roche/Genentech, Sanofi, Servier and Xbiotech. Please see the abstract for all other authors’ relevant financial disclosures.