The results from COMBI-d and COMBI-v clinical trials were presented at the 2019 American Society of Clinical Oncology ( ASCO ) Annual Meeting and published simultaneously in The New England Journal of Medicine ( NEJM ).
The first-line treatment with Dabrafenib ( Tafinlar ) and Trametinib ( Mekinist ) 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 Dabrafenib plus Trametinib survived at five years.
19% ( 95% CI: 15-22% ) of patients showed no sign of disease progression or death at five years.
Five-year overall survival ( OS ) and progression-free survival ( 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, represent 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 Dabrafenib plus Trametinib.
Of patients who achieved a complete response with Dabrafenib plus Trametinib, 19% ( n=109 ) had five-year PFS and OS rates of 49% and 71%, respectively, compared with 19% and 34% in the overall population.
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 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.
COMBI-d is a pivotal phase III randomized, double-blinded study comparing the combination of the BRAF inhibitor, Dabrafenib, and the MEK inhibitor, Trametinib, to single-agent therapy with Dabrafenib and placebo as first-line therapy in patients with unresectable ( stage IIIC ) or metastatic ( stage IV ) BRAF V600E/K mutation-positive cutaneous melanoma.
The study randomized 422 patients from 121 investigative sites.
COMBI-v is a two-arm, open-label, phase III study comparing the combination of Dabrafenib plus Trametinib with Vemurafenib monotherapy in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma. The primary endpoint of this study was overall survival. ( Xagena )
Source: Novartis, 2019