Episode 9: First data from CheckMate 8WH investigating double immunotherapy as a first line treatment in MSI-H/dMMR metastatic colon cancer

The upcoming episode for WND in GI cancer will focus on the groundbreaking CheckMate 8HW trial in MSI-H/dMMR metastatic colorectal cancer patients. This phase 3 trial involved randomization between double immunotherapy with NIVO and IPI versus NIVO alone or the SOC with chemotherapy plus targeted therapy for clinical benefit in first-line treatment.

At ASCO GI2024, the results were presented for the comparison between double immunotherapy and SOC. The primary endpoint was PFS, with key secondary endpoints being safety and response rate. The trial achieved complete PFS with a remarkable HR of 0.21, indicating a reduction of almost 80% in the risk for PFS.

The median PFS was not reached for the double immunotherapy group, whereas it was nearly 6 months for the chemotherapy group. The 2-year PFS for patients was 74% compared to only 14% in the chemotherapy group, showcasing impressive outcomes. Safety signals remained consistent with earlier findings, with fewer side effects noted in the double immunotherapy group compared to chemotherapy and targeted therapy.

These significant findings are expected to revolutionize the current treatment regimen for these patients. Currently, the SOC consists of pembrolizumab monotherapy, so the experts await the comparison with the NIVO monotherapy arm. Given the results of KEYNOTE-177, one can anticipate the benefits of combined therapy. All subgroups of patients show PFS benefits, in contrast to earlier findings with immunotherapy in the KEYNOTE 177 trial. The potential impact of this study is practice-changing, and experts eagerly await more mature data.