Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, I.N.T. IRCCS Fondazione "G. Pascale" Napoli, Naples, Italy.
Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy.
J Clin Oncol. 2023 Jan 10;41(2):212-221. doi: 10.1200/JCO.21.02961. Epub 2022 Sep 1.
Limited prospective data are available on sequential immunotherapy and BRAF/MEK inhibition for -mutant metastatic melanoma.
SECOMBIT is a randomized, three-arm, noncomparative phase II trial (ClinicalTrials.gov identifier: NCT02631447). Patients with untreated, metastatic -mutant melanoma from 37 sites in nine countries were randomly assigned to arm A (encorafenib [450 mg orally once daily] plus binimetinib [45 mg orally twice daily] until progressive disease [PD] -> ipilimumab plus nivolumab [ipilimumab 3 mg/kg once every 3 weeks and nivolumab 1 mg/kg once every 3 weeks × four cycles -> nivolumab 3 mg/kg every 2 weeks]), arm B [ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib], or arm C (encorafenib plus binimetinib for 8 weeks -> ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib). The primary end point was overall survival (OS) at 2 years. Secondary end points included total progression-free survival, 3-year OS, best overall response rate, duration of response, and biomarkers in the intent-to-treat population. Safety was analyzed throughout sequential treatment in all participants who received at least one dose of study medication.
A total of 209 patients were randomly assigned (69 in arm A, 71 in arm B, and 69 in arm C). At a median follow-up of 32.2 (interquartile range, 27.9-41.6) months, median OS was not reached in any arm and more than 30 patients were alive in all arms. Assuming a null hypothesis of median OS of ≤ 15 months, the OS end point was met for all arms. The 2-year and 3-year OS rates were 65% (95% CI, 54 to 76) and 54% (95% CI, 41 to 67) in arm A, 73% (95% CI, 62 to 84) and 62% (95% CI, 48 to 76) in arm B, and 69% (95% CI, 59 to 80) and 60% (95% CI, 58 to 72) in arm C. No new safety signals emerged.
Sequential immunotherapy and targeted therapy provide clinically meaningful survival benefits for patients with -mutant melanoma.
针对 - 突变型转移性黑色素瘤，有限的前瞻性数据可用于序贯免疫治疗和 BRAF/MEK 抑制。
SECOMBIT 是一项随机、三臂、非对照的 II 期临床试验（ClinicalTrials.gov 标识符：NCT02631447）。来自 9 个国家 37 个地点未经治疗的转移性 - 突变型黑色素瘤患者被随机分配至 A 组（康奈非尼 [450 mg 口服，每日一次] 联合比美替尼 [45 mg 口服，每日两次]，直至疾病进展 [PD] -> 伊匹单抗联合纳武单抗 [伊匹单抗 3 mg/kg，每 3 周一次，纳武单抗 1 mg/kg，每 3 周一次 × 4 个周期 -> 纳武单抗 3 mg/kg，每 2 周一次]）、B 组（伊匹单抗联合纳武单抗直至 PD -> 康奈非尼联合比美替尼）或 C 组（康奈非尼联合比美替尼治疗 8 周 -> 伊匹单抗联合纳武单抗直至 PD -> 康奈非尼联合比美替尼）。主要终点为 2 年总生存率（OS）。次要终点包括总无进展生存期、3 年 OS、最佳总体缓解率、缓解持续时间和意向治疗人群中的生物标志物。对所有接受至少一剂研究药物的参与者，在整个序贯治疗中进行安全性分析。
共有 209 名患者被随机分配（A 组 69 例，B 组 71 例，C 组 69 例）。在中位随访 32.2 个月（四分位距，27.9-41.6）时，任何组均未达到中位 OS，所有组均有超过 30 名患者存活。假设 OS 中位数≤15 个月的假设为零，所有组均达到 OS 终点。A 组 2 年和 3 年 OS 率分别为 65%（95%CI，54 至 76）和 54%（95%CI，41 至 67），B 组分别为 73%（95%CI，62 至 84）和 62%（95%CI，48 至 76），C 组分别为 69%（95%CI，59 至 80）和 60%（95%CI，58 至 72）。未出现新的安全性信号。
序贯免疫治疗和靶向治疗为 - 突变型黑色素瘤患者提供了具有临床意义的生存获益。
