Treatment With Dabrafenib, Trametinib Demonstrates High Relapse-free Survival Rate in Melanoma Patients

More than half of high-risk patients with resected, stage III BRAF V600-mutated melanoma who were treated with dabrafenib (Tafinlar, Novartis) and trametinib (Mekinist, Novartis) were alive and relapse-free at 5 years, according to a recent study published in The New England Journal of Medicine.

Each year, more than 285,000 cases of melanoma are diagnosed globally, with approximately half having a BRAF mutation. Following surgical treatment for stage III melanoma, patients may have a risk of recurrence because melanoma cells could still be present in the body.

Additionally, the authors noted that allowing high-risk patients with stage III melanoma to be relapse-free at 5 years is significant due to the disease often causing relapses in that 5-year period.

“Findings published today offer confidence that treatment with dabrafenib and trametinib following surgery provides a durable, long-term relapse-free survival benefit for those at high risk of cancer recurrence,” said Reinhard Dummer, MD, professor and vice chairman of the Department of Dermatology at the University Hospital of Zurich, in a press release. “These findings add to the growing body of evidence demonstrating the clinical value of dabrafenib and trametinib in the adjuvant setting.”

The results from the COMBI-AD trial demonstrated that 52% of patients treated with dabrafenib and trametinib were alive and relapse-free at 5 years compared with 36% of patients who received the placebo. The median relapse-free survival (RFS) was not reached in the dabrafenib and trametinib arm of the study, compared with a median RFS of 16.6 months in the placebo arm.

Based on the data, the researchers found that patients treated with dabrafenib and trametinib had a 49% reduced risk of relapse or death compared with the placebo. Additionally, the researchers found that the RFS from treatment with dabrafenib and trametinib was generally consistent across all substages of the disease, based on AJCC-7 criteria.

A secondary endpoint in the study, the 5-year distant metastasis-free survival (DMFS) rate, was 65% in patients treated with dabrafenib and trametinib compared with 54% in patients who received the placebo.

The assessment for overall survival (OS) is currently ongoing, although the OS analysis at the first interim showed a 3-year OS rate of 86% in the dabrafenib and trametinib arm compared with 77% in the placebo arm. Furthermore, the OS results favored the combination therapy with dabrafenib and trametinib over placebo, but the researchers noted that their prespecified interim significance threshold of P = 0.000019 was not met in the study.

“Reaching the 5-year mark without relapse is a profound moment for a patient living with high-risk, stage III melanoma,” said Jeff Legos, PhD, MBA, senior vice president and head of oncology drug development at Novartis Oncology, in a press release. “Tafinlar plus Mekinist has helped patients and clinicians reimagine what is possible for patients living with advanced melanoma. We are proud of the deep and durable benefit demonstrated in COMBI-AD and remain grateful to the patients, investigators and their families who participated in this clinical trial.”

All patients who participated in the trial completed their therapy in the extended follow-up period. During this period, the researchers assessed the reported adverse events (AEs) from patients and found that there was no clinically meaningful difference between the dabrafenib and trametinib arm and placebo arm in the occurrence or severity of serious AEs.

REFERENCE

Novartis Tafinlar® + Mekinist® demonstrates long-term, relapse-free survival benefit for high-risk, stage III melanoma patients in study published in NEJM. Basel, Switzerland: Novartis; September 16, 2020. novartis.com/news/media-releases/novartis-tafinlar-mekinist-demonstrates-long-term-relapse-free-survival-benefit-high-risk-stage-iii-melanoma-patients-study-published-nejm. Accessed September 22, 2020.