What You Need to Know
Michael Atkins M.D., national lead Investigator, and Andrew Pecora M.D., co-investigator, participated in completing the phase III DREAM seq trial that generated results that will guide the practice of care globally for patients with advanced BRAF mutated melanoma.
The study was published in the September 27, 2022 issue of the Journal of Clinical Oncology.
Dr. Atkins and Dr. Andrew Pecora at the John Theurer Cancer Center campus worked collaboratively through the NCI designated consortium with other national investigators in this randomized trial that showed a significant survival advantage among patients with BRAF-mutated advanced melanoma who received combined (anti PD-1 and anti CTLA-4) checkpoint inhibitor therapy as the first line of therapy followed by targeted therapy with dabrafenib and trametinib on progression as compared with patients with BRAF-mutated melanoma who first received targeted therapy followed by checkpoint inhibitor therapy on progression.
About the Study
About half of melanoma cases carry mutations in key proteins that control cell growth, such as BRAF, which can be targeted with a combination of dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor). Immunotherapy boosts the power of the immune system to fight cancer. Targeted medications and immunotherapy have become standard care for people with advanced melanoma. But one of the biggest questions in oncology has been determining the best sequence of treatments.
Starting in 2015, 265 patients with metastatic melanoma were randomly assigned to one of two groups. One group started treatment with combination ipilimumab and nivolumab immunotherapy, and the second group began with the targeted therapies dabrafenib and trametinib. Two-year overall survival was 72% among patients who received combination immunotherapy first versus 52% for those who took the two targeted therapies as initial treatment. Progression-free survival, where the cancer remains stable or improves, also tended to be better for the immunotherapy group.
The new study provides strong evidence demonstrating how best to treat patients with advanced melanoma that contains a BRAF V600E mutation: immunotherapy is the better initial approach, even for people whose tumors have a mutation that could be treated by targeted therapies.