Novartis announced results from the landmark 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[1]. 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[1],[4].
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. These data were presented at the 2019 ASCO Annual Meeting (Abstract #9507) and published simultaneously in The New England Journal of Medicine[1],[4].
"Our analysis demonstrates that first-line therapy with Tafinlar + Mekinist leads to five-year disease control in about one-fifth of the patients and five-year survival in about one-third of those treated," said Caroline Robert, MD, Ph.D., Head of the Dermatology Unit at the Institut Gustave Roussy in Paris. "While metastatic melanoma has historically had a very poor prognosis for patients, there are many reasons to be encouraged today. Our analysis demonstrates a clinically meaningful and positive impact on patient survival. These results show that targeted therapies may provide long-term survival and offer durable outcomes."
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.
"The five-year COMBI-d/v analysis is truly gratifying, as it shows us that many BRAF+ melanoma patients on Tafinlar + Mekinist are living much longer than what may have been expected when originally diagnosed," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "Other Novartis-sponsored melanoma research at ASCO this week illustrates our drive to do even more in melanoma. Efficacy results from the study of the immunotherapy spartalizumab were encouraging as the oncology community learns more about how immunotherapies may be combined with established targeted therapies to provide an even greater benefit to patients."
About COMBI-d and COMBI-v
COMBI-d is a pivotal Phase III randomized, double-blinded study (NCT01584648) comparing the combination of the BRAF inhibitor, Tafinlar, and the MEK inhibitor, Mekinist, to single-agent therapy with Tafinlar 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 Tafinlar + Mekinist with vemurafenib monotherapy in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma (NCT01597908). The primary endpoint of this study was OS[1].
Efficacy Findings for Investigational Anti-PD-1 Antibody Spartalizumab (PDR001) Used in Combination With Tafinlar + Mekinist Also Reported
Also presented at ASCO were findings from the COMBI-i study evaluating Tafinlar + Mekinist in combination with spartalizumab in metastatic melanoma patients with...
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