Novartis today announced data from the Phase III COMBI-d study showing a significant survival benefit for patients with BRAF V600E/K mutation-positive metastatic melanoma when treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) compared to Tafinlar monotherapy alone.

This is the first combination of BRAF/MEK inhibitors to demonstrate a statistically significant overall survival benefit for this patient population in two Phase III studies. Results are being presented today at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

"This final analysis from COMBI-d confirms prior results showing a statistically significant improvement in overall survival among patients with BRAF V600E/K mutation-positive metastatic melanoma receiving the combination of dabrafenib and trametinib compared to dabrafenib monotherapy," said Georgina Long, B.Sc., Ph.D., M.B.B.S., F.R.A.C.P., medical oncologist, Melanoma Institute Australia, The University of Sydney.

"These findings further reinforce the rationale for the treatment of metastatic melanoma with this combination."

The final analysis included the 423 patients enrolled in COMBI-d and showed that the combination of Tafinlar and Mekinist achieved a statistically significant overall survival (OS) benefit compared to Tafinlar monotherapy (median of 25.1 months vs 18.7 months)[1].

The analysis for the combination also showed median progression-free survival (PFS) of 11.0 months, overall response rate (ORR) of 69%, and median duration of response (DoR) of 12.9 months[1]. The safety results were consistent with the profile observed to date for the combination and consistent with the profile observed for Tafinlar monotherapy; no new safety concerns were observed[1].

The most common adverse events (>=20%) in the combination arm were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, joint pain (arthralgia), hypertension, vomiting, cough and peripheral edema[1].

"We are very pleased to have entered into a new disease area with the acquisition of two medicines that are making a positive impact on the lives of people with this serious form of skin cancer," said Bruno Strigini, President, Novartis Oncology.

"These COMBI-d data prove that these medicines can significantly extend the lives of people with BRAF V600E/K mutation-positive melanoma, and we are proud to be part of the progress in this disease."

In addition to results from the COMBI-d study, long-term data from a Phase I-II study showed a three-year OS rate of 38% (95% CI, 25%, 51%) after treatment with the combination of Tafinlar and Mekinist in all patients with BRAF V600 E/K mutation-positive metastatic melanoma. Safety results from this study were consistent with those observed in other trials evaluating the combination.

Other data being presented at the meeting, including oral presentations related to the investigational use of dabrafenib and trametinib, include studies in BRAF V600E-mutated metastatic colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and other rare cancers.

The results from the COMBI-d study are also being published online in The Lancet on May 31.