COMBI-d and COMBI-v phase III trials of Tafinlar + Mekinist in melanoma published in NEJM.

Novartis announced results from the landmark phase III COMBI-d and COMBI-v clinical trials, concluding that first-line treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) offers both overall and progression-free long-term survival benefits to patients with unresectable or metastatic BRAF-mutation positive melanoma. Researchers reported that 34% (95% CI: 30-38%) of all patients in the pooled analysis who were treated with Tafinlar + Mekinist survived at five years. Study authors also reported on prolongation in progression-free survival (PFS), with 19% (95% CI: 15-22%) of patients showing no sign of disease progression or death at five years. Five-year overall survival and PFS were similar in the pooled patient population.

The results, from a pooled analysis of 563 patients from the COMBI-d and COMBI-v trials, represented the largest collection of data and longest follow-up among patients with advanced melanoma with BRAF V600-mutated unresectable or metastatic melanoma who were treated with Tafinlar + Mekinist. Of patients who achieved a complete response with Tafinlar + Mekinist, 19% (n=109) had five-year PFS and overall survival rates of 49% and 71%, respectively, compared with 19% and 34% in the overall population. Researchers also observed that the efficacy of subsequent treatment was preserved in patients who progressed on study treatment and subsequently received immune checkpoint inhibitor therapy.

Adverse events (regardless of causality) were reported in 548 of 559 patients (98%) with no new safety signals. Adverse events (AEs) led to permanent discontinuation of study treatment in 99 of 559 patients (18%); the most common events were pyrexia (4%), decreased ejection fraction (4%) and increased alanine aminotransferase (1%). No treatment-related deaths were reported in patients treated with dabrafenib plus trametinib. These data were presented at the 2019 ASCO Annual Meeting (Abstract #9507) and published simultaneously in The New England Journal of Medicine.

See: "Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma" Caroline Robert et al. NEJM June 4, 2019 DOI: 10.1056/NEJMoa1904059