A combination of the immune checkpoint inhibitors Opdivo (nivolumab) and Yervoy (ipilimumab) induces durable responses in patients with metastatic colorectal cancer with certain genetic features, a Phase 2 clinical trial shows.
The trial, CheckMate-142 (NCT02060188), examined the combination in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer, two genetic features that make cancers more aggressive, but also more responsive to immunotherapies.
The findings were presented in January at the 2018 Gastrointestinal Cancers Symposium in San Francisco, California. The oral presentation was titled “Nivolumab + ipilimumab combination in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC): First report of the full cohort from CheckMate-142.”
The genetic abnormalities in tumors with MSI-H and dMMR impair cells’ ability to repair DNA. This leads to an accumulation of mutations in tumor cells, which sometimes generate structurally different proteins that the immune system identifies as malignant.
Keytruda (pembrolizumab), another immune checkpoint inhibitor, is already approved for cancers with these genetic abnormalities, which led researchers to test the combination of Opdivo and Yervoy.
The trial included 119 patients with dMMR or MSI-H metastatic colorectal cancer. Most – 76 percent – had received at least two prior lines of therapy. Its primary measure was the proportion of patients who responded to the treatment, as assessed by the investigators. Additional measures included duration of response, overall survival, progression-free survival, and safety.
After a median follow-up of 13.4 months, 55 percent of patients had responded to the treatment. The clinical responses were durable, with 94 percent of responses still ongoing at the time of data cutoff.
At one year, 85 percent of patients were still alive, and 71 percent were progression-free.
“These results demonstrate that Opdivo plus Yervoy provide durable clinical benefit in patients with dMMR or MSI-H metastatic colorectal cancer,” Thierry André, MD, head of the Medical Oncology Department in St. Antoine Hospital, Assistance Publique Hôpitaux de Paris and lead author of the study, said in a press release.
“The combination of Opdivo and Yervoy may represent an important advance for these distinct biomarker-defined patients, who historically have poorer outcomes compared to metastatic colorectal cancer patients whose tumors are mismatch repair proficient or microsatellite stable,” André said.
The treatment was safe overall, with 32 percent of patients reporting severe or life-threatening treatment-related adverse events. Only 13 percent discontinued treatment due to these side effects. No new safety signals or treatment-related deaths were reported.
“The Opdivo and Yervoy combination has demonstrated efficacy across tumors in a broad range of patients, and we are very encouraged to see that the complementary effect of this combination has the potential to increase anti-tumor activity in patients with dMMR or MSI-H metastatic colorectal cancer,” said Ian M. Waxman, MD, development lead, gastrointestinal cancers, at Bristol-Myers Squibb, sponsor of the trial.
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