Expanding targeted therapy to NRAS-mutated melanoma
Mené sur 71 patients atteints d'un mélanome avancé présentant une mutation du gène NRAS ou la mutation Val600 du gène BRAF, cet essai de phase II évalue l'efficacité, du point de vue de la proportion de patients avec réponse objective, et la toxicité d'un inhibiteur de MEK1/2 appelé MEK162
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. 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% CI 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. Treatment seemed to be well tolerated, with 13 (43%) patients with NRAS-mutated melanoma having a grade 3—4 adverse event, most commonly oedema, diarrhoea, rash, dermatitis, and generally asymptomatic increases in creatine phosphokinase. Only four (13%) patients with NRAS-mutated melanoma discontinued therapy because of an adverse event...
The Lancet Oncology , commentaire en libre accès, 2012