Dabrafenib/Trametinib Combo Shows Long-Term Survival Benefit in Metastatic Melanoma

First-line treatment with dabrafenib (Tafinlar) and trametinib (Mekinist) provided overall survival (OS) and long-term progression-free survival (PFS) benefits in patients with unresectable or metastatic BRAF-mutation positive melanoma, according to a pooled analysis of 2 phase 3 trials.

Metastatic melanoma often results in poor prognosis for patients who are diagnosed. Each year, there are approximately 280,000 new diagnoses of melanoma, approximately half of which have BRAF mutations, according to Novartis.

Dabrafenib plus trametinib is currently approved for indications in melanoma and non-small cell lung cancer.

The analysis combined data of 563 patients from the COMBI-d and COMBI-v trials, representing the largest collection of data and longest follow-up among patients with BRAF-mutated metastatic melanoma.

COMBI-d evaluated the combination of dabrafenib, a BRAF inhibitor, and trametinib compared with single-agent therapy with dabrafenib and a placebo as first-line therapy in 422 patients. In COMBI-v, dabrafenib plus trametinib was evaluated in comparison with vemurafenib monotherapy in the same patient population.

According to the analysis, 34% (95% CI: 30%-38%) of all patients in both studies who were treated with dabrafenib plus trametinib reached 5-year survival. Additionally, 19% (95% CI: 15%-22%) of patients showed no sign of disease progression or death at 5 years. Five-year OS and PFS were similar in the pooled patient population.

Adverse effects (AEs) were reported in 98% of patients, with no new safety signals. Eighteen percent of patients in the analysis permanently discontinued study treatment due to AEs.

“Our analysis demonstrates that first-line therapy with Tafinlar + Mekinist leads to 5-year disease control in about one-fifth of the patients and 5-year survival in about one-third of those treated,” Caroline Robert, MD, PhD, head of the dermatology unit at the Institute Gustave Roussy, said in a press release. “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.”

In another study, the COMBI-I phase 3 trial, dabrafenib and trametinib were compared with the same combination therapy plus the immunotherapy spartalizumab as first-line therapy in patients with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma.

These data were presented at the 2019 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine.

Reference

Long-term survival benefit shown for metastatic melanoma patients treated with Novartis Tafinlar + Mekinist [news release]. Novartis. https://www.novartis.com/news/media-releases/long-term-survival-benefit-shown-metastatic-melanoma-patients-treated-novartis-tafinlar-mekinist. Accessed June 18, 2019.