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

 

• COMBI-AD is first trial to demonstrate 5-year relapse-free survival with targeted therapy as adjuvant treatment in high-risk patients with stage III BRAF-mutated melanoma¹
   
• Adjuvant treatment with standard-of-care targeted therapy Tafinlar + Mekinist reduced the risk of relapse or death by 49% compared to placebo¹
   
• Updated data show Tafinlar + Mekinist improved distant metastasis-free survival, a secondary endpoint¹

             
Basel, September 16, 2020 — Novartis announced previously reported data from the Phase III COMBI-AD study were published today 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 years¹. Research suggests the majority of relapses in high-risk stage III melanoma generally occur within 5 years^1,2.

“Findings published today offer confidence that treatment with dabrafenib and trametinib following surgery provides a durable, long-term relapse-free survival benefit for those at high risk of cancer recurrence,” said Prof. Reinhard Dummer, M.D., Vice Chairman of the Department of Dermatology, University Hospital of Zurich. “These findings add to the growing body of evidence demonstrating the clinical value of dabrafenib and trametinib in the adjuvant setting.”

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])¹. 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.