The use of first-line immunotherapy combination with Opdivo (nivolumab) and low-dose Yervoy (ipilimumab) continues to show robust, long-term benefit in patients with microsatellite instability high (MSI-H) or with mismatch repair-deficient (dMMR) metastatic (spreading) colorectal cancer, according to new study results presented at the 2020 ASCO annual meeting.
In the CheckMate-142 study, the average length of response, average time without disease progression, and the average overall survival had not yet been reached with the immunotherapy combination after an average follow-up of 29 months, reported lead investigator Heinz-Josef Lenz, MD, FACP, Co-Director, GI Oncology Program, University of Southern California Norris Comprehensive Cancer Center, Los Angeles.
“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/dMMR metastatic colorectal cancer who receive their first treatment with chemotherapy have poor outcomes, he said. The nivolumab-ipilimumab combination already showed effectiveness in patients who have received previous therapies in the CheckMate-142 study. Based on those data, nivolumab alone or in combination with ipilimumab was approved by the FDA for the treatment of patients with colorectal cancer whose disease progressed after chemotherapy with oxaliplatin and irinotecan.
Results from CheckMate-142
An earlier analysis (at an average of 13.8 months) of outcomes from the CheckMate-142 study in patients with MSI-H/dMMR colorectal cancer who received the immunotherapy combination as their first-line treatment showed long-term benefits.
CheckMate-142 is an ongoing multi-group, non-randomized phase 2 study. In the single-arm study, patients received nivolumab every 2 weeks and ipilimumab every 6 weeks, until their disease progressed or until they had to discontinue the treatment.
Between the early analysis and the current analysis presented at the ASCO meeting, “the majority of patients experienced a deepening of response,” Dr. Lenz said. A total of 84% patients had a reduction in tumor burden from baseline. At 24 months, the average time without disease progression was 74% and the average overall survival was 79%.
The study population included 45 patients with colorectal cancer; 38% of them had metastatic disease with BRAF mutations, 22% had KRAS mutations, and 18% had Lynch syndrome. At the time of the analysis, 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 because of an adverse event related to the treatment.
At the latest follow-up, the objective response rate was 69%, an increase from 60% at the earlier analysis of an average of 13.8-month follow-up. The complete response rate at 29-month average follow-up was 13% (compared with 7% at 13.8 months), which included 3 additional patients with a complete response and 1 additional patient with a partial response since July 2018. The disease control rate was 84% at the latest analysis. Of the 45 patients, 15 (33%) were still receiving the study treatment, 11 were off treatment and received subsequent therapies, and 19 patients were treatment-free. Of these 19 off-treatment patients, 14 had at least 1 tumor assessment during the treatment-free interval; 2 of these patients had a complete response, 7 had a partial response, and 1 had stable disease.
The side effects with the immunotherapy combination remained similar with longer follow-up, and no new safety issues were reported at the latest follow-up.
Nivolumab plus ipilimumab remained well-tolerated, with 22% of patients having serious (grade 3 or 4) treatment-related side effects, and only 7% of patients discontinued treatment because of serious side effects, said Dr. Lenz.
- A study of treatment with nivolumab and ipilimumab in 45 patients with metastatic colorectal cancer led to robust and durable outcomes
- At the end of the study, 33% of the patients were still receiving treatment, 11 were off treatment and were receiving subsequent therapies, and 19 were treatment-free
- At 24 months, the average time without disease progression was 74% and the average overall survival was 79%