Phase III COMBI-v study shows survival benefits for Tafinlar (dabrafenib) + Mekinist (trametinib) in metastatic melanoma- Novartis

Novartis announced updated data from the Phase III COMBI-v study showing a significant overall survival benefit for patients with BRAF V600E/K mutation-positive metastatic melanoma when treated with the combination of Tafinlar (dabrafenib) + Mekinist (trametinib) compared to Zelboraf (vemurafenib) monotherapy. In the COMBI-v study, the dabrafenib/trametinib combination achieved a statistically significant overall survival (OS) benefit compared to vemurafenib monotherapy (median for the combination 25.6 months vs 18.0 months). The rate of OS at two years was 51% for those receiving the dabrafenib/trametinib combination and 38% for those receiving vemurafenib monotherapy.

In addition, the median overall response rate was 65.6% in patients receiving the dabrafenib/trametinib combination compared to 52.8% for those receiving vemurafenib monotherapy. The safety results from this study were consistent with the profile observed to date for the combination; no new safety concerns were observed. Results were presented at the European Cancer Congress 2015 in Vienna.

Comment: The significant overall survival benefit of dabrafenib/trametinib from COMBI-v is consistent with the results demonstrated by the combination in COMBI-d, another Phase III trial previously reported at the American Society of Clinical Oncology annual meeting earlier in 2015. The dabrafenib/trametinib combination is seen as an answer to resistance problems faced by the monotherapies. The commercial limitations on the combination are its narrow market: BRAF V600E mutation patients (around half of metastatic melanoma patients) and competition from Keytruda (pembrolizumab) and Opdivo (nivolumab), with their impressive data across all melanoma types.