CheckMate -8HW Trial Data Show Survival Improvement With Opdivo, Yervoy Combo in Colorectal Cancer

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The combination of Bristol Myers Squibb’s Opdivo (nivolumab) with Yervoy (ipilimumab) showed significant improvements in progression-free survival (PFS) as a first-line treatment for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC)in the Phase III CheckMate -8HW trial. The combination produced a 79% reduction in the risk of disease progression or death compared to chemotherapy, according to the trial.

“Patients with MSI-H/dMMR metastatic colorectal cancer are less likely to benefit from chemotherapy,” said Thierry Andre, MD, head of the medical oncology department, Sorbonne University, Hospital Saint-Antoine, Paris, France, in a press release. “An impressive improvement in PFS and sustained benefit beginning at three months was observed with nivolumab plus ipilimumab versus chemotherapy in this trial. These results demonstrate the meaningful efficacy of this combination with practice-changing potential for this patient population.”

Opdivo, a PD-1 immune checkpoint inhibitor, has been approved for indications that include melanoma, non-small cell lung cancer, and colorectal cancer. The combination of Opdivo and Yervoy, a recombinant human monoclonal antibody, was the first immune-oncology combination approved by the FDA for metastatic melanoma, and has been approved in more than 50 countries. The combination is also indicated for the first-line treatment of adults with unresectable advanced or metastatic esophageal squamous cell carcinoma, hepatocellular carcinoma, intermediate or poor risk advanced renal cell carcinoma, unresectable malignant pleural mesothelioma, and non-small cell lung cancer.

The results of CheckMate -8HW, presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, showed improvements to PFS at approximately three months into treatment and continued through the duration of the trial.

The randomized, open-label trial analyzed Opdivo plus Yervoy vs. Opdivo monotheray or investigator’s choice chemotherapy, with mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab. Investigators randomly assigned 830 patients to receive either Opdivo monotherapy, Opdivo plus Yervoy, or investigator’s choice of chemotherapy.

Median PFS had not been reached in the Opdivo plus Yervoy cohort (95% CI: 38.4-NE) compared with 5.9 months in the chemotherapy cohort (95% CI: 4.4-7.8). The PFS benefit was consistent across all pre-specified subgroups, which includes patients with KRAS or NRAS mutations, and in patients with baseline liver, lung, or peritoneal metastases.

In terms of safety, the combination showed a profile consistent with what has previously been observed in clinical trials, with no new safety signals found. Treatment-related adverse events (TRAEs) were reported in 23% of those treated with the combination compared to 48% of those who were given chemotherapy.

“With research from the full CheckMate clinical development program, BMS has revolutionized the oncology landscape and helped change survival expectations for people with cancer. Today, with these data from CheckMate -8HW, we showed that Opdivo plus Yervoy reduced the risk of disease progression or death by an unprecedented 79%,” said Dana Walker, MD, MSCE, VP, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. “These results build on the benefit of Opdivo and Yervoy in MSI-H/dMMR metastatic colorectal cancer as previously demonstrated in CheckMate -142 and reinforce our commitment to exploring the potential of these therapies to help more patients in need."

The CheckMate-8HW trial is currently in progress to assess PFS in patients administered Opdivo plus Yervoy compared to Opdivo monotherapy across all lines of therapy.

References

Opdivo (nivolumab) Plus Yervoy (ipilimumab) Reduced the Risk of Disease Progression or Death by 79% Versus Chemotherapy in Patients with Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer in CheckMate -8HW Trial. Bristol Myers Squibb. January 20, 2024. Accessed January 22, 2024. https://news.bms.com/news/corporate-financial/2024/Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Reduced-the-Risk-of-Disease-Progression-or-Death-by-79-Versus-Chemotherapy-in-Patients-with-Microsatellite-Instability-High-or-Mismatch-Repair-Deficient-Metastatic-Colorectal-Cancer-in-CheckMate--8HW-Trial/default.aspx