Dr. Patel on the Sequencing of Immunotherapy and Targeted Therapy in BRAF-Mutant Melanoma

Sapna Patel, BA, MD, a medical oncologist, an associate professor, and the director of the Uveal Melanoma Program and Melanoma Fellowship Program at The University of Texas MD Anderson Cancer Center, discusses the sequencing of immunotherapy and targeted therapy in BRAF-mutant melanoma.

Although targeted therapy is a treatment option for patients with unresectable BRAFV600–mutant melanoma, results from the phase 3 DREAMseq trial (NCT02224781) demonstrated that treatment with immunotherapy followed by targeted therapy improved overall survival compared with targeted therapy followed by immunotherapy. Patients enrolled in DREAMseq were randomly assigned to receive the immunotherapy combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) followed by the targeted therapy combination of dabrafenib (Tafinlar) and trametinib (Mekinist), or the converse sequence.

Patients who received the immunotherapy before the targeted therapy experienced a 2-year OS rate of 71.8%, compared with 51.5% for those who received the immunotherapy after the targeted therapy. Although a small number of patients can do poorly with immunotherapy prior to targeted therapy, the trial established this sequence as the standard for this patient population, Patel says

In the neoadjuvant setting, this sequence could yield similar results, Patel continues. According to a pooled analysis from the International Neoadjuvant Melanoma Consortium found that pathologic complete responses (pCRs) and major CRs to immunotherapy were long lasting; however, pCRs and major CRs to BRAF/MEK therapy still led to relapses or recurrence, Patel says. Although no head-to-head trials have been conducted in the neoadjuvant setting, treatment decisions could trend toward immunotherapy prior to target therapy.

In the adjuvant setting, both immunotherapy and target therapy have displayed efficacy. An important piece of real-world evidence is that patients given adjuvant PD-1 therapy can experience recurrence while on therapy, Patel explains. Recurrences while on BRAF/MEK therapy are less common; however, relapses can occur after discontinuation.

Based on this real-world evidence, targeted therapy could be used first in the adjuvant setting to pursue a cure. Otherwise, frontline immunotherapy has demonstrated benefits in the neoadjuvant and metastatic settings, Patel concludes.