On January 22, BMS released encouraging findings from the CheckMate -8HW clinical study, showcasing Opdivo (nivolumab) combined with Yervoy (ipilimumab) as a front-line treatment choice for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). BMS presented this data backing its immune checkpoint inhibitor (ICI) combination for newly diagnosed patients with a subtype of progressive colorectal cancer at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. Currently, the standard of care (SOC) for CRC is slowly shifting from fluorouracil-containing chemotherapies to targeted therapies and immunotherapies; however, addressing mCRC poses significant challenges due to considerable unmet needs in effective treatment.
The open-label, randomised Phase III CheckMate -8HW trial front-line cohort enrolled 303 participants who were randomly allocated to one of three groups: those receiving nivolumab monotherapy, the combination of nivolumab + ipilimumab, or chemotherapy. Following a median follow-up of 24.3 months, the median progression-free survival (PFS) remained indeterminate among 171 patients administered nivolumab + ipilimumab, while it was 5.8 months for 84 patients subjected to standard therapy. This discrepancy between the two groups corresponds to a noteworthy 79% reduction in the risk of disease progression or mortality associated with the utilisation of the dual ICI regimen (hazard ratio [HR] 0.21, 95% confidence interval [CI] [0.14, 0.32]; P < 0.0001). The comprehensive safety analysis also demonstrated a preference for the ICI combination over chemotherapy, albeit with a distinct spectrum of adverse events. In total, grade 3/4 treatment-related adverse events (TRAE) occurred in 23% of patients receiving the dual ICI regimen, contrasting with 48% in the chemotherapy arm, with or without targeted therapy. The occurrence of grade 3/4 serious TRAE was identical at 16% in both treatment arms. Furthermore, discontinuation of therapy due to TRAE was noted in 17% of patients undergoing dual ICI treatment, in contrast to 32% among those subjected to standard therapy. Notably, two treatment-related deaths were documented in the dual ICI group, while none occurred in the chemotherapy arm.
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Opdivo is expected to directly compete with MSD’s PD-1 inhibitor Keytruda (pembrolizumab), granted first-line monotherapy approval for MSI-H/dMMR colorectal cancer in 2020, which notably achieved $2bn in sales last year according to GlobalData’s patient-based forecast. Concurrently, Opdivo is expected to experience a modest increase in total annual sales, from $2bn in 2023 to $2.4bn in 2031. This marginal increase is attributed to the impending patent expiration in 2026 in the EU and 2028 in the US. Although Keytruda’s patent also expires in 2028, its first-to-market position confers higher expected sales than Opdivo. Nonetheless, in indirect comparison, Opdivo + Yervoy exhibits more robust data than Keytruda, whereby in the KEYNOTE-177 trial, Keytruda monotherapy reduced the risk of progression or mortality by 40% compared to chemotherapy, whether administered alone or in combination with targeted therapies, in previously untreated MSI-H/dMMR colorectal cancer. Nivolumab + ipilumumab demonstrated a substantial 79% risk reduction compared to chemotherapy, marking a noteworthy improvement.
