A biomarker analysis of CheckMate76 data showed that baseline tumor mutation burden and interferon gamma signal are associated with a higher benefit of nivolumab.
Patients with resected stage IIA/B/C melanoma face a 5-year risk for recurrence of 24% to 43%. The CheckMate76 study (NCT04099251) evaluated the efficacy and safety of adjuvant nivolumab for 12 months in patients with resected stage IIB/C melanoma. Recently published results showed that adjuvant nivolumab significantly increased recurrence-free survival (HR, 0.42; P<0.0001).
Georgina Long, PhD, and colleagues performed an exploratory biomarker analysis to determine patient subgroups that have a high risk for recurrence (prognostic biomarkers) and to understand the benefit of adjuvant nivolumab treatment in biomarker-defined subgroups of patients (predictive biomarkers). Dr. Long and colleagues presented these findings at the 2023 ASCO Annual Meeting, held June 2-6 in Chicago.
In CheckMate76, 790 patients were randomly assigned 2:1 to either adjuvant nivolumab or placebo. Baseline biomarkers were obtained from primary tumor biopsy (ie, interferon gamma [IFNγ] signal, tumor mutation burden [TMB], BRAFv600 status, percentage CD8 T cells, PD-L1 expression, and tumor mitotic rate [TMR]) and from serum (ie, C-reactive protein [CRP]). Analyses were performed within each treatment arm and comparing nivolumab with placebo treatment.
Within the nivolumab arm a higher IFNγ signal, TMB, and CD8 T cell count, and lower serum CRP were associated with improved recurrence-free survival. Within the placebo arm, none of the biomarkers tested was prognostic for recurrence-free survival.
In addition, a higher IFNγ signal, TMB, CD8 T cell count, and lower serum CRP were predictive of the benefit of nivolumab versus placebo. For example, patients with a high IFNγ signal had more benefit from nivolumab versus placebo (HR, 0.29) compared with patients with a low IFNγ signal (HR, 0.44).
In a multivariate analysis, tumor stage and CRP level at baseline proved to be the strongest independent prognostic biomarkers in this population. TMB and IFNγ signal were the strongest independent predictive biomarkers.
Based on these results, Dr. Long concluded that “among all the biomarkers tested, TMB and IFNγ signal had the largest independent effect of the relative benefit of nivolumab over placebo.”
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