Dr Petrella on Selecting Frontline Therapy in Metastatic Melanoma

“The DREAMseq and SECOMBIT trials have told us that using the combination of nivolumab and ipilimumab [results in better outcomes compared] with giving targeted therapy, first. Based on all that data, this is pretty much [how] our first-line therapies for patients with metastatic melanoma have [come into being].”

Teresa Petrella, MD, MHSc, FRCPC, medical oncologist, affiliate scientist, Evaluative Clinical Sciences, Odette Cancer Research Program, Sunnybrook Research Institute; and associate professor, Department of Medicine, University of Toronto, discusses key considerations in selecting frontline therapy for patients with metastatic melanoma based on long-term survival data and therapeutic sequencing findings.

Over the past decade, multiple studies have evaluated the efficacy of combination immunotherapy with nivolumab (Opdivo) and ipilimumab (Yervoy) compared with single-agent checkpoint inhibitors. Updated 10-year results from the phase 3 CheckMate 067 trial (NCT01844505) continue to demonstrate a survival benefit with combination therapy, with overall survival (OS) rates of 43% for nivolumab plus ipilimumab, 37% for nivolumab monotherapy, and 19% for ipilimumab monotherapy. Petrella notes that these findings indicate that the benefit of combination therapy remains durable beyond the 3-year mark.

Beyond treatment with CTLA-4 and PD-1 blockade, Petrella explains that data from the phase 2/3 RELATIVITY-047 trial (NCT03470922)of nivolumab plus relatlimab-rmbw (Opdualag), a LAG-3 inhibitor, demonstrated a progression-free survival (PFS) advantage vs nivolumab alone in this patient population (HR, 0.79; 95% CI, 0.66-0.95). Investigators observed a trend in favor of the combination for OS (HR, 0.80; 95% CI, 0.66-0.99), with 3-year OS rates of 55% (95% CI, 49.2%-59.6%) and 48% (95% CI, 42.7%-53.1%), respectively.

Petrella adds that therapeutic sequencing trials, including the phase 2 SECOMBIT (NCT02631447) and phase 3 DREAMseq (NCT02224781) trials have also provided additional insights into the optimal order of systemic therapy in metastatic melanoma.

Findings from these studies suggest that initiating treatment with combination immunotherapy, rather than targeted therapy, leads to superior long-term outcomes, she explains. In patients with BRAF-mutated disease, early use of immune checkpoint blockade has been associated with prolonged survival compared with targeted therapy.

Given the evolving treatment landscape of this disease, Petrella explains that combination immunotherapy remains the preferred first-line approach for eligible patients, providing the potential for durable responses and long-term survival benefits.