Lynn Mara Schuchter, MD, the C. Willard Robinson Professor of Hematology-Oncology and Program Leader of the Melanoma Program at Abramson Cancer Center of the University of Pennsylvania, Philadelphia, commented at a press briefing that the study “will ultimately be practice-changing.” She noted, “This has been a very difficult disease to treat, and the MEK inhibitors make biological sense.”

The paper’s formal discussant, Michael A. Davies, MD, PhD, Assistant Professor in the Department of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, commented on the “interesting” finding that patients who lack the activating GNAQ or GNA11 mutations nevertheless derived clinical benefit. “So it would not be rational to exclude these patients from future clinical trials of these pathway inhibitors,” he said.

Speaking to a packed ballroom, Dr. Davies reflected back on the advances seen in this disease in the past several years. “I remember my first ASCO in 2005, and the melanoma oral abstract session, where you clearly had no trouble getting a seat. The most memorable part of the session was a debate between presenters as to whose data was ‘the most spectacularly negative’. Now, when the 2013 ASCO schedule came out, I was somewhat disappointed that the streak of plenary presentations on melanoma had been broken. However; this disappointment was tempered by the recent approval of two more agents for patients with metastatic melanoma.”

‘Landmark’ Study

The study by Carvajal et al “truly is the first randomized trial to demonstrate improvement in clinical outcomes in patients with metastatic uveal melanoma, and this is a landmark,” he noted. “The question now is how to build upon this initial activity.”

He suggested that future studies attempt to characterize the patients with wild-type GNAQ/11 who also responded to selumetinib, pharmacodynamically evaluate the drug’s effect on the MEK pathway, and characterize the compensatory signaling events and tumor biology upon disease progression in order to identify and prioritize rational combinatorial approaches. ■

Disclosure: Dr. Davies is on the advisory board of GlaxoSmithKline, Roche/Genentech, and Novartis. He also receives research funding from AstraZeneca, GlaxoSmithKline, Roche/Genentech, Merck, Oncothyreon, and Myriad.