Nivolumab plus ipilimumab improves PFS in MSI-H/dMMR metastatic colorectal cancer

Elaine Soliven
02 Feb 2024
metastatic colorectal cancer, mCRC, nivolumab, ipilimumab, MSI-H, dMMR, CheckMate 8HW trial

First-line dual immunotherapy combination of nivolumab (NIVO) and ipilimumab (IPI) demonstrates a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy among patients with MSI-H/dMMR* metastatic colorectal cancer (mCRC), according to the CheckMate 8HW trial presented at ASCO GI 2024.

The initial results of the CheckMate 8HW phase III trial showed a 79-percent reduction in the risk of disease progression or death with NIVO plus IPI compared with standard chemotherapy in this patient population. [ASCO GI 2024, abstract LBA768]

“The trial met its primary endpoint,” said lead author Dr Thierry Andre from Sorbonne Université and Hôpital Saint Antoine in Paris, France.

CheckMate 8HW trial included 303 patients with MSI-H/dMMR mCRC who were randomized to receive either NIVO plus IPI** (n=202) or the investigator’s choice of chemotherapy*** (n=101). Of these, 85 percent and 83 percent, respectively, of the participants had centrally confirmed MSI-H/dMMR status at baseline.

After a median follow-up of 24.3 months, the median PFS was not reached in the NIVO plus IPI arm and was 5.9 months in the chemotherapy arm (hazard ratio, 0.21; p<0.0001).

Additionally, patients treated with NIVO plus IPI compared with chemotherapy had a higher PFS rate at 12 months (79 percent vs 21 percent), which was maintained through 24 months (72 percent vs 14 percent).

Notably, the PFS benefit observed with NIVO plus IPI was consistent across all prespecified subgroups, including KRAS or NRAS mutation status and baseline liver, lung, or peritoneal metastases.

In terms of safety, NIVO plus IPI recipients had fewer grade ≥3 treatment-related adverse events than chemotherapy recipients (23 percent vs 48 percent).

The safety profile of NIVO plus IPI was consistent with the established profiles of each drug; no new safety signals were identified, Andre noted.

“Overall, NIVO plus IPI demonstrated superior PFS over chemotherapy in patients with centrally confirmed MSI-H/dMMR mCRC,” said Andre. “Results support NIVO plus IPI as a standard-of-care first-line treatment option for patients with MSI-H/dMMR mCRC.”

“These exciting results from the CheckMate 8HW study have potentially practice-changing implications for previously untreated patients with MSI-H/dMMR mCRC,” Andre said in a press release. “Additional data may help define the further benefit of the combination of nivolumab and ipilimumab compared to nivolumab alone and [this may] help oncologists determine the best treatment options for their patients.”

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