Dermatology Department, IUCT Oncopole, Toulouse.
Biostatistic Unit, DRCI Léon Berard Centre, Lyon.
Melanoma Res. 2022 Aug 1;32(4):269-277. doi: 10.1097/CMR.0000000000000833. Epub 2022 May 27.
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.
考比替尼联合维莫非尼于 2015 年在法国通过“临时用药授权”（TAU，在 2016 年上市前预批准使用）方案获批用于治疗 v-raf 鼠肉瘤病毒致癌基因同源物 B1 突变型晚期黑色素瘤患者。本研究旨在为先前在 TAU 登记的患者提供真实世界的结果。这项非干预性、前瞻性、多中心的法国研究，在先前登记在 TAU 的患者中进行，旨在评估总生存期（OS）和无进展生存期（PFS），并描述联合治疗的耐受性。在首次服用考比替尼（与维莫非尼联合使用）时，185 例可评估患者中有 88%为 IV 期疾病（脑转移：其中 70%），31%的患者乳酸脱氢酶升高，10%的患者东部肿瘤协作组（ECOG）指数≥2。中位 OS 为 16.1 个月（95%CI，12.5-20.7）。脑转移（P<0.001）、ECOG 指数≥2（P=0.007）和肝功能损害（P=0.037）是与较短生存期显著相关的独立因素。中位 PFS 为 7.3 个月（95%CI，5.2-8.4）。ECOG 指数≥2（P=0.006）与较短的 PFS 显著相关。在开始服用考比替尼和纳入研究之间，最常见的严重不良事件为肌酸磷酸激酶升高（3%的患者）、视网膜浆液性脱离（3%）、左心室射血分数降低（3%）、转氨酶升高（3%）和皮疹（3%）。本研究在法国为 BRAF 突变型晚期黑色素瘤患者提供了维莫非尼联合考比替尼的真实世界结果。我们的数据倾向于在真实环境中证实，这种联合治疗对这类患者是有效的，且安全性与之前的干预性研究一致。
