The Use of Dual Targeted Therapy in Metastatic Melanoma

Source: OncLive, August 2019

The data for the COMBI studies are very interesting. COMBI-d was a study where dabrafenib and trametinib was compared with dabrafenib alone in patients with melanoma in the first line. And COMBI-v was a study where dabrafenib and trametinib was compared with vemurafenib, which is another BRAF inhibitor. And so these 2 COMBI studies were presented initially in 2014 and 2015, and what they showed is that there’s a marked benefit basically to the combination of dabrafenib and trametinib to either vemurafenib or to dabrafenib alone. Either way, there’s a marked benefit.

Now, what we have recently is a long-term analysis of progression-free survival and survival. And essentially what’s been shown in this combination study, which has over 950 patients, is that you can have extremely prolonged progression-free survival and overall survival basically beyond 3 years. The progression-free survival curve seems to flatten out, and patients who have not had progression at 3 years can expect to stay pretty much in the same status up to about 5 years. And that’s roughly a fifth of all patients. So roughly 20% of patients will have prolonged disease control on the dabrafenib-trametinib combination. And if you look at overall survival, that number looks even better.

COMBI progression-free survival data are interesting in another way. The progression-free survival was 49% in patients who had a complete response, or CR. And so that’s interesting that, in a sense, once you’ve had a CR on treatment with dabrafenib and trametinib, it’s very likely that those patients followed longitudinally will have no evidence of progression in 5 years. It’s just based on a number. So that’s another important thing to consider.