Novartis Tafinlar + Mekinist demonstrates long-term, relapse-free survival benefit for high-risk, stage III melanoma patients in study published in NEJM.- Novartis

Novartis announced previously reported data from the Phase III COMBI-AD study were published in The New England Journal of Medicine . The study shows more than half of high-risk patients with resected, stage III BRAF V600-mutated melanoma treated with Tafinlar (dabrafenib) + Mekinist (trametinib) were alive and relapse-free at 5 years. Research suggests the majority of relapses in high-risk stage III melanoma generally occur within 5 years. Results showed 52% of patients (95% CI, 48-58%) treated with Tafinlar + Mekinist were alive and relapse-free at 5 years compared to 36% of patients (95% CI, 32-41%) who received placebo. Median relapse-free survival (RFS) was not reached in the Tafinlar + Mekinist arm (95% CI, 47.9 months-NR) compared to 16.6 months (95% CI, 12.7-22.1 months) in the placebo arm. Treatment with Tafinlar + Mekinist reduced the risk of relapse or death by 49% compared to placebo (hazard ratio, HR, 0.51 [95% CI, 0.42-0.61]). These findings were presented at the 2020 ASCO Virtual Scientific Program. A subgroup analysis showed a generally similar RFS benefit across all substages, as assessed by AJCC-7 criteria. The five-year distant metastasis-free survival (DMFS) rate, a secondary endpoint, was 65% (95% CI, 61-71%) in patients treated with Tafinlar + Mekinist compared to 54% (95% CI, 49-60%) in patients who received placebo. COMBI-AD is ongoing to assess the secondary endpoint of overall survival (OS); the OS analysis at the first interim analysis showed a 3-year OS rate of 86% in the Tafinlar + Mekinist arm compared to 77% in the placebo arm. Overall survival results favored the combination therapy with Tafinlar + Mekinist over placebo, but the prespecified interim significance threshold of P = 0.000019 was not met. See-Dummer R, Hauschild A, Santinami M et al. "Five-Year Relapse-Free Survival With Adjuvant Dabrafenib Plus Trametinib in Stage III BRAF-Mutant Melanoma". New England Journal of Medicine. 2020; 377(19):1813-1823.