CheckMate 8HW is an international, open-label study of nivolumab plus ipilimumab vs nivolumab monotherapy or chemotherapy in 839 patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (mCRC). In the first interim analysis (published in 2024), nivolumab plus ipilimumab improved progression-free survival (PFS) compared with chemotherapy. Recently published in The Lancet, Prof Thierry André and colleagues shared the results of the updated analysis from CheckMate 8HW evaluating nivolumab plus ipilimumab vs nivolumab monotherapy across all lines of therapy.
The dual immune checkpoint inhibitors demonstrated a significant PFS benefit and a significantly higher response rate compared with nivolumab monotherapy. Median PFS was not reached in the nivolumab plus ipilimumab arm and was 39.3 months for the nivolumab arm. Estimated proportions of patients in the nivolumab plus ipilimumab group who were alive and progression-free were 76% at 12 months, 71% at 24 months, and 68% at 36 months. Treatment discontinuation due to disease progression was reported in 23% of patients receiving dual immunotherapy and 39% of those receiving nivolumab monotherapy. There was a higher incidence of treatment-related adverse events in the nivolumab plus ipilimumab arm, but the authors suggest the safety profile is manageable, with no new safety signals reported. The most common treatment-related adverse events were pruritus, diarrhea, and hypothyroidism.
The authors also shared the longer follow-up results of PFS with nivolumab plus ipilimumab vs chemotherapy in the first-line setting. Patients receiving the dual immunotherapy continued to show PFS benefit vs chemotherapy, with a median PFS of 54.1 months.
High level
The results from the CheckMate 8HW trial showed clinically meaningful improvement in PFS with the use of dual immune checkpoint inhibitors in the treatment of microsatellite instability-high or mismatch repair-deficient mCRC. Given that this patient group is reportedly more resistant to immune checkpoint inhibitors, broad adoption of validated immunohistochemistry and polymerase chain reaction-based testing is important. Future investigations might include analyses of progression-free and overall survival by best overall response, as well as biomarker analyses assessing correlations between radiographic response and circulating tumor DNA.
Ground level
According to the study authors, these results support nivolumab plus ipilimumab as a potential new standard of care for patients with microsatellite instability-high or mismatch repair-deficient mCRC across lines of therapy. Clinicians should be aware that there was a higher incidence of immune-mediated endocrine adverse events reported in the nivolumab plus ipilimumab group, most of which were grade 1 and 2. Despite these differences, patients receiving nivolumab plus ipilimumab or nivolumab monotherapy reported improvements from baseline in health-related quality of life. Overall survival data from the CheckMate 8HW trial are expected in the future and will help to further contextualize the results of this study.
