Novartis announced data from a Phase III study showing a significant survival benefit for patients with BRAF V600E/K mutation-positive advanced melanoma when treated with the first-line combination of Tafinlar® (dabrafenib) + Mekinist® (trametinib) compared to Tafinlar monotherapy. The results from the COMBI-d three-year follow-up analysis represent one of the longest survival follow-up studies to date with BRAF mutation-positive advanced melanoma patients. Results are being presented today at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
“BRAF mutation remains the critical genetic feature in advanced melanoma that guides patients’ treatment options,” said Keith T. Flaherty, MD, Director of the Henri and Belinda Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center and Professor of Medicine, Harvard Medical School. “These results confirm that long-term survival can be achieved with this combination and it should be an important consideration for patients with BRAF mutation-positive advanced melanoma. It is particularly striking to note the excellent outcome for those with lower burden of disease at baseline.”
Results from the COMBI-d study of 423 patients found the estimated three-year survival rate to be 44% for patients receiving the combination of Tafinlar + Mekinist (95% CI, 36.4%-50.5%) compared with 32% who received Tafinlar alone (95% CI, 25.4%-38.3%). There were 26 patients who crossed over from the monotherapy arm to the combination arm after the combination demonstrated a significant overall survival (OS) benefit in a prior analysis. Additionally, the estimated three-year progression-free survival rate was 22% (95% CI, 16.2%-28.0%) for the combination arm and 12% (95% CI, 7.1%-18.0%) for the monotherapy arm. In an analysis of patients with normal lactate dehydrogenase (LDH) levels and fewer than three disease sites, the three-year survival rate for combination was 62% (95% CI, 49.3%-72.0%) compared with 45% who received Tafinlar alone (95% CI, 34.9%-55.1%). In advanced melanoma, a patient’s LDH level is often predictive of prognosis and may be a predictor of treatment response.
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. The most common adverse events (>=20%) in the combination arm were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, vomiting, joint pain (arthralgia), hypertension, cough and peripheral edema.
“Novartis is committed to improving outcomes for advanced melanoma patients, and we are gratified to see that these data show that we are extending the lives of many patients receiving therapy with Tafinlar + Mekinist,” said Alessandro Riva, MD, Global Head, Oncology Development & Medical Affairs. “This data is also a strong example of the importance of rationally combining targeted therapies and identifying those patients who are likely to benefit from our medicines beyond three years. This type of treatment approach is not only helping to grow the practice of precision oncology, but has the potential to fundamentally change the way we treat cancer.”