Survival in adult patients with BRAFV600 mutation-positive advanced melanoma: a noninterventional ambispective study of patients with cobimetinib combined with vemurafenib during the French early access program: MELANIS study. Issue 4 (27th May 2022)

• Record Type: Journal Article
• Authors: Meyer, Nicolas; Pérol, David; Duval-Modeste, Anne-Bénédicte; El Adaoui, Laïla; Lelarge, Yoann; Niarra, Ralph; Mateus, Christine
• Is Part Of: Melanoma research. Volume 32:Issue 4(2022)
• Page Start: 269
• Page End: 277
• Publication Date: 2022-05-27
• Subjects: BRAF -- cobimetinib -- melanoma -- observational study -- survival -- vemurafenib; Melanoma -- Periodicals; Melanoma -- Periodicals; Melanomen; 616.99477
• DOI: 10.1097/CMR.0000000000000833
• Languages: English
• ISSNs: 0960-8931

Abstract

Abstract : Cobimetinib combined with vemurafenib was available in France in 2015 through a 'Temporary Authorization for Use' program (TAU, preapproval access pending its marketing on 2016) for patients with v-raf murine sarcoma viral oncogene homolog B1-mutant advanced melanoma. This study aimed to provide real-world outcomes in patients previously registered in this TAU. This noninterventional, ambispective, multicentre French study, conducted in patients previously registered in TAU, aimed to estimate overall survival (OS) and progression-free survival (PFS) and to describe the tolerability of the therapeutic combination. At first cobimetinib intake (in combination with vemurafenib), 88% of the 185 evaluable patients had disease stage IV (brain metastasis: 70% of them), 31% had elevated lactate dehydrogenases, and 10% had an Eastern Cooperative Oncology Group (ECOG) index ≥2. Median OS was 16.1 months (95% CI, 12.5–20.7). Brain metastasis ( P < 0.001), ECOG index ≥2 ( P = 0.007), and hepatic impairment ( P = 0.037) were found as independent factors significantly associated with shorter survival. Median PFS was 7.3 months (95% CI, 5.2–8.4). ECOG index ≥2 ( P = 0.006) was significantly associated with shorter PFS. Between cobimetinib start and inclusion, increased CPK (3% of patients), retinal serous detachment (3%), decreased left ventricular ejection fraction (3%), increased transaminases (3%), and rash (3%) were the most reported serious adverse events. This study provides real-world outcomes in France for the vemurafenib-cobimetinib combination available in patients with BRAF-mutant-advanced melanoma. Our data tend to confirm in the real-life setting that this combination therapy is effective in such patients, with a safety profile consistent with previous interventional studies.