Immunotherapy Before Targeted Therapy Improves Survival in Advanced Melanoma
Source: Inside Precision Medicine, September 2022
Combination PD-1/CTLA-4 blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with BRAF V600 mutant metastatic melanoma. However, little prospective data existed to guide the choice of initial therapy or sequence in these patients. In a paper in the Journal of Clinical Oncology researchers conducting the DREAMseq (EA6134) trial appear to have provided convincing data that treatment order—with immunotherapy first over targeted therapy—leads to survival benefits.
The randomized phase III DREAMseq trial involving 265 people with advanced melanoma showed that if there was disease progression, starting treatment with combination PD-1/CTLA-4 immunotherapy (nivolumab and ipilimumab), followed by targeted BRAF/MEK therapy (dabrafenib and trametinib) led to a clinically meaningful 20% improvement in 2-year overall survival from the start of treatment when compared to the opposite treatment sequence (72% vs. 52%, respectively). Progression-free survival, where the cancer is stable or improving, was also trending in favor of those who started on immunotherapy.
The DREAMseq (EA6134) trial sought to improve survival for patients found with stage 3 or 4 skin cancer that had spread beyond its local area and could not be removed by surgery. To be eligible, patients needed to have BRAF V600 mutations in the tumor cells. These mutations drive cancer growth and are present in roughly 40% to 50% of melanomas.