Expanding targeted therapy to NRAS-mutated melanoma

摘要

In The Lancet Oncology, Paolo Ascierto and colleagues report a phase 2 study of 71 patients with metastatic melanoma whose tumours harboured either activating BRAF mutations (41 patients) or NRAS mutations (30 patients), treated with a highly selective, allosteric MEK1/2 inhibitor, MEK162.1 Although activity was noted in patients with BRAF-mutated melanoma who had not previously received a BRAF inhibitor, the key findings of the study were that six (20%) patients with NRAS-mutated melanoma had a partial response, and 19 (63%) achieved disease control. Median progression-free survival (PFS) was 3-7 months (95% Cl 2-5-5-4) and median duration of response was a modest 7-6 weeks (range 0-1-17-3) for patients with NRAS-mutated melanoma. Surprisingly, three of six partial responses were unconfirmed, with one subsequently confirmed, one progressing, and one unstated. No complete responses were attained, but of great interest were two patients with NRAS mutations who had untreated brain metastases and showed evidence of regression in their brain tumours with MEK162.