Paul D. Nathan, MBBS, PhD, FRCP, consultant medical oncologist, Mount Vernon Cancer Centre, discusses the long-term outcomes with the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) in patients with 

 V600-mutant unresectable or metastatic melanoma.

Five-year follow-up data presented at the 2019 ASCO Annual Meeting showed a progression-free survival rate of 19% and an overall survival rate of 34% with the combination in this patient population. Notably, of the 19% patients who achieved a complete response (CR) to the combination, 49% were progression-free and 71% were alive at 5 years.

 V600 mutations are amenable to BRAF/MEK inhibition, says Nathan. Those who have favorable baseline characteristics and achieve a CR early on in treatment are likely to derive the greatest long-term benefit from the combination, he added. Given these results, molecular testing for BRAF has become integral to practice. Notably, testing can be sent for in the stage III setting and there are also potent BRAF-directed therapies in the adjuvant setting, concludes Nathan.

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Paul D. Nathan, MBBS, PhD, FRCP, consultant medical oncologist, Mount Vernon Cancer Centre, discusses the long-term outcomes with the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) in patients with BRAF V600-mutant unresectable or metastatic melanoma.

Dr. Nathan on Long-Term Outcomes With Dabrafenib/Trametinib in BRAF V600-Mutant Melanoma

Paul D. Nathan, MBBS, PhD, FRCP, consultant medical oncologist, Mount Vernon Cancer Centre, discusses the 5-year analysis of the COMBI-d and COMBI-v trials, which look at the long-term effects of dabrafenib (Tafinlar) plus trametinib (Mekinist) in patients with 

 V600—mutant unresectable or metastatic melanoma.

At the 5-year follow-up, the progression-free survival rate was 19% and the overall survival rate was 34%. There is a cohort of patients who do well on the combination long term, according to Nathan. Now, physicians must figure out how to identify who is going to respond well to the combination at the baseline. Physicians have corroborated some earlier data based on a multivariate analysis and a regression tree analysis, looking at baseline characteristics to identify who is likely to do well, according to Nathan.

Physicians found some markers that are associated with durability of response, including whether someone has a normal lactate dehydrogenase, fewer than 3 organ sites involved, and a good performance status. The most powerful marker of durability of response is whether somebody has a complete response (CR) to treatment. However, that is not a baseline marker; rather, it is a marker that is generated while a patient is on treatment. In the trial, 19% of patients had a CR to treatment. In the 5-year outcome for the patients who had a CR, 49% were progression free and 71% were alive at 5 years.

Paul D. Nathan, MBBS, PhD, FRCP, discusses the 5-year analysis of the COMBI-d and COMBI-v trials, which look at the long-term effects of dabrafenib plus trametinib in patients with BRAF V600–mutant unresectable or metastatic melanoma.

Paul D. Nathan, MBBS, PhD, FRCP

Articles

Dr. Nathan on Long-Term Outcomes With Dabrafenib/Trametinib in BRAF V600-Mutant Melanoma

Dr. Nathan on 5-Year Survival Outcomes of COMBI-d and COMBI-v Trials in BRAF V600-Mutant Melanoma