Dr. Seedor on Treatment Sequencing in Metastatic Melanoma

Rino S. Seedor, MD, assistant professor, Sidney Kimmel Cancer Center, Jefferson Health, discusses findings from the phase 3 DREAMseq trial (NCT02224781), which solidified up-front immunotherapy followed by targeted therapy upon progression as a standard of care in patients with BRAF V600–mutant metastatic melanoma.

The DREAMseq trial investigated whether dabrafenib (Tafinlar) plus trametinib (Mekinist) followed by ipilimumab (Yervoy) plus nivolumab (Opdivo) or the immunotherapies followed by the targeted therapies resulted in improved outcomes for patients with stage III-IV BRAF V600–mutant melanoma.

In the past, patients with BRAF-mutated melanoma had the option of receiving frontline immunotherapy or targeted therapy upon progression, although the benefits of starting treatment with 1 or the other were unknown, Seedor says. The DREAMseq trial showed that patients who received immunotherapy prior to targeted therapy had better outcomes than those who received targeted therapy before immunotherapy, Seedor explains. Specifically, at a median follow-up of 27.7 months, patients who first received ipilimumab plus nivolumab had a 2-year overall survival rate of 72% vs 52% in those who first received dabrafenib plus trametinib.

These data confirm the efficacy of a common treatment method, demonstrating that all patients with advanced melanoma, even those with BRAF mutations, should first receive immunotherapy, followed by targeted therapy in the presence of a targetable alteration upon progression, Seedor concludes.