Trials and Treatment in Advanced Melanoma

Source: OncLive, October 2019

Hussein A. Tawbi, MD, PhD: COMBI-AD was a large, randomized, global phase III trial that took patients with nodal involvement, so stage III patients—it was patients with stage IIIa, IIIb, and IIIc in the AJCC [American Joint Committee on Cancer Cancer Staging Manual] 7th edition—and randomized them to dabrafenib and trametinib as active therapy versus placebo. Treatment was conducted for a year. Over 800 patients were randomized, and the study actually had a very long follow-up.

I can tell you that in the field, we have waited very patiently to see the results of that study. It was really useful to see the results, because after a prolonged follow-up—I believe it was over 22½ years at the time of first reporting—the combination of dabrafenib and trametinib was highly effective and decreased the risk of recurrence with a hazard ratio of 0.47, which is almost a 53% reduction in the risk of relapse. There was also an improvement in overall survival.

I was careful not to say significant, because it had a really low P value. It was 0.000-something, but it hadn’t hit the primary level for significance for that study. That was set originally by the statistical design and then, with a longer follow-up that was reported in the Journal of Clinical Oncology, it was interesting to see that based on a cure-rate model, the combination is actually capable of curing patients—up to almost 17% of patients.