BRAF/MEK Combo Yields 'Impressive' 5-Year Survival in Melanoma

Jeffrey S. Weber, MD, PhD


September 16, 2019

This transcript has been edited for clarity.

I'm Dr Jeffrey Weber, a medical oncologist at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health here in New York City.

I want to discuss an abstract Paul Nathan presented at the recent 2019 meeting of the American Society of Clinical Oncology.[1] This abstract reported the 5-year follow-up of the phase 3 trials called COMBI-d and COMBI-v, which compared dabrafenib plus trametinib, the BRAF and MEK drugs, with dabrafenib alone (COMBI-d); and dabrafenib plus trametinib with vemurafenib (COMBI-v), which was then a standard-of-care therapy.

Dr Nathan discussed the outcomes of the 563 patients with unresectable or metastatic melanoma who had received dabrafenib plus trametinib in both trials. The median progression-free survival (PFS) in those patients was 11.1 months, which is quite similar to what we've seen with most of our BRAF-MEK drugs. The 5-year PFS was 19%. If you break it down by lactate dehydrogenase (LDH) levels, the PFS goes up to 25% for those with normal baseline LDH levels, but only 8% for those with baseline LDH levels elevated above normal. And if you go to the very select group of those with normal baseline LDH levels and fewer than three organ sites with metastases, the PFS is 31%.

The important data, of course, is the fact that 62% of patients have died. And a significant proportion of patients actually went on to get other immunotherapies. But the 5-year overall survival is 34%, or about one third of patients, which is significant. You see what appears to be a plateau suggesting that about one third of patients who start out with the BRAF-MEK drugs, dabrafenib and trametinib, will do well in the long term.

Breaking it down by the LDH level, 43% of patients with a normal LDH survived to 5 years, compared with only 16% of those with an LDH above the upper limit of normal. For those patients in that select population with normal LDH levels and fewer than three metastatic sites, the overall survival at 5 years was 55%, which is a respectable number. At 5 years, 19% were complete responders, and the total, best overall response rate at the end of the day was 68%. The PFS for the complete responders was about 49% at 5 years, and overall survival for the complete responders at 5 years was an impressive 71%. Again, as in many histologies with many therapies, it's always the complete responders who do well.

So, what do we conclude? You can have 5-year disease control in about one quarter of patients when you use dabrafenib and trametinib. Patients will be alive, doing well, with many in remission—one third of those at 5 years—and a good proportion of these may well be cured, although a number of patients will eventually receive immunotherapies. The urban legend that all patients who receive dabrafenib and trametinib will progress and all will die by 5 years is not true. That 34% 5-year survival is an impressive proportion.

Feel free to send us your questions or concerns. This is Dr Jeffrey Weber. Thank you for your attention.

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