5-year follow-up demonstrates long-term benefit of dabrafenib/trametinib for stage 3 melanoma

June 4, 2020

Results presented at the recent ASCO 2020 Virtual Scientific Program demonstrate the long-term relapse-free and survival benefit of dabrafenib (Tafinlar, Novartis) and trametinib (Mekinist, Novartis) as a combination treatment following surgery in stage III BRAF V600E/K-mutant melanoma patients.

Some patients with melanoma may have a better chance at a longer, relapse-free life using a combination therapy following surgery, according to results from a prospective analysis of a study that investigated dabrafenib (Tafinlar, Novartis) and trametinib (Mekinist, Novartis) in patients with high-risk resected stage 3 BRAF V600E/K-mutant melanoma.

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Researchers reported that more than half of patients treated with adjuvant dabrafenib plus trametinib after surgical removal of melanoma were alive and relapse-free at five years.1 Relapse-free survival (RFS) rates were 52% (95% CI, 48%-58%) with the dual therapy vs 36% (95% CI, 32%-41%) with placebo. The updated results of the COMBI-AD study were presented at The American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program held May 29-31, which included data from a 5-year follow-up period.

Researchers report the placebo group results were consistent to that of standard melanoma relapse-free survival rates in patients with resected stage 3 melanoma and have gone without treatment.1

Also, median RFS was not reached by the five-year cut-off for dabrafenib and trametinib patients, pointing to a possible long-term benefit in the post-surgical setting, while median RFS for placebo patients was 16.6 months (95% CI, 12.7-22.1 mo), according to a press release.1 Researchers also report the combination treatment reduced the risk of relapse or death by 49% vs placebo (hazard ratio [HR] 0.51; 95% CI 0.42, 0.61).

“Our goal as clinicians is to give our stage 3 patients the best chance for relapse-free survival,” says Axel Hauschild, M.D., professor of dermatology at the University Hospital Schleswig-Holstein, Germany. “Results from COMBI-AD show that adjuvant treatment with Tafinlar plus Mekinist after surgical resection gives melanoma patients the chance for long-term relapse-free survival. Five years is a clinically and emotionally significant milestone for patients. Recurrent BRAF positive melanoma, once spread to other organs, can be more dangerous and difficult to treat. The durable, long-term results seen among patients in the COMBI-AD trial clearly point to the important role targeted therapy plays in the adjuvant setting.”

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The combination treatment was given a breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) in December 2017 for the adjuvant treatment of BRAF V600E or V600K mutated melanoma, and was later approved on April 30, 2018.2

The COMBI-AD study is a randomized, two-arm, double-blind phase 3 trial that evaluated dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) as a combination treatment versus matching placebos in 870 patients with resected stage 3 BRAF V600E/K-mutant melanoma and who had not had previous anticancer therapy.

“The five-year survival mark is an important and predictive milestone for people with melanoma and the doctors who care for them,” says John Tsai, M.D., head of Global Drug Development and chief medical officer at Novartis. “We see an almost 50% risk reduction in melanoma relapse or death in the COMBI-AD data announced today, and we believe patients will find this information helpful in choosing a treatment after surgery. We thank the patients and their families who participated in this long-term clinical trial. Their participation and commitment is helping the community learn how a BRAF-targeted therapy can reimagine outcomes for patients with resectable stage 3 melanoma.”

References:

1. Novartis International AG. (2020, May 29). Novartis announces long-term, relapse-free survival benefit for high-risk, stage III melanoma patients treated with Tafinlar® + Mekinist® following surgery. Retrieved June 04, 2020, from https://www.globenewswire.com/news-release/2020/05/29/2040879/0/en/Novartis-announces-long-term-relapse-free-survival-benefit-for-high-risk-stage-III-melanoma-patients-treated-with-Tafinlar-Mekinist-following-surgery.html
2. Novartis receives FDA approval of Tafinlar® + Mekinist® for adjuvant treatment of BRAF V600-mutant melanoma. (2018, April 30). Retrieved June 04, 2020, from https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-tafinlar-mekinist-adjuvant-treatment-braf-v600-mutant-melanoma