Ba He, Zhu Fangyuan, Zhang Xiaoze, Mei Zubing, Zhu Yaodong
Department Chinese and Western Medicine Integrated Oncology, the First Affiliated Hospital of Anhui Medical University, No. 120 Wansui Road, Hefei 230000, Anhui Province, China.
Department of Anorectal Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China.
Ther Adv Med Oncol. 2023 Jan 24;15:17588359221148918. doi: 10.1177/17588359221148918. eCollection 2023.
Although immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatment for resected melanoma, the optimal therapy remains controversial. Therefore, we conducted this updated network meta-analysis (NMA) to assess the efficacy and tolerability of adjuvant therapies for cutaneous melanoma.
PubMed, Embase, Cochrane library, and Web of Science were systematically searched for relevant literatures published in the last 30 years. Disease-free survival (DFS), overall survival (OS), and serious adverse events were considered as the efficacy and tolerability outcomes.
In all, 27 randomized controlled trials (RCTs) including 16,709 stage III-IV melanoma patients were enrolled in this NMA. For BRAF wild-type melanoma, our analysis showed that both nivolumab and pembrolizumab demonstrated significantly better DFS and tolerability than ipilimumab (10 mg/kg). Nivolumab, pembrolizumab, ipilimumab (3 mg/kg), and ipilimumab (10 mg/kg) all appeared to be effective in prolonging OS, but no therapy demonstrated significantly better OS than ipilimumab (10 mg/kg). Nivolumab + ipilimumab showed the best DFS, but did not appear to be effective in improving OS and ranked only seventh in tolerability. Vaccines and granulocyte-macrophage colony-stimulating factor therapies were well tolerated, but all failed to improve the DFS or OS in stage III melanoma patients. In terms of BRAF mutation-positive melanoma, ICIs (nivolumab + ipilimumab, nivolumab, pembrolizumab, ipilimumab; 10 mg/kg) exhibited comparable efficacy to dabrafenib + trametinib, and all these therapies showed significantly better DFS than placebo.
Considering efficacy and tolerability, nivolumab and pembrolizumab seem to be preferable adjuvant therapies for patients with stage III-IV melanoma. For BRAF mutation-positive patients, more RCTs are still required to determine which is better between ICIs and targeted therapy.
尽管免疫检查点抑制剂（ICIs）和靶向治疗已被广泛用作切除黑色素瘤的辅助治疗，但最佳治疗方案仍存在争议。因此，我们进行了这项更新的网络荟萃分析（NMA），以评估皮肤黑色素瘤辅助治疗的疗效和耐受性。
系统检索了PubMed、Embase、Cochrane图书馆和Web of Science，以获取过去30年发表的相关文献。无病生存期（DFS）、总生存期（OS）和严重不良事件被视为疗效和耐受性结果。
本NMA共纳入27项随机对照试验（RCT），包括16709例III-IV期黑色素瘤患者。对于BRAF野生型黑色素瘤，我们的分析表明，纳武单抗和帕博利珠单抗在DFS和耐受性方面均显著优于伊匹单抗（10mg/kg）。纳武单抗、帕博利珠单抗、伊匹单抗（3mg/kg）和伊匹单抗（10mg/kg）在延长OS方面似乎均有效，但没有一种治疗方案在OS方面显著优于伊匹单抗（10mg/kg）。纳武单抗+伊匹单抗显示出最佳的DFS，但在改善OS方面似乎无效，在耐受性方面仅排名第七。疫苗和粒细胞-巨噬细胞集落刺激因子疗法耐受性良好，但均未能改善III期黑色素瘤患者的DFS或OS。就BRAF突变阳性黑色素瘤而言，ICIs（纳武单抗+伊匹单抗、纳武单抗、帕博利珠单抗、伊匹单抗；10mg/kg）与达拉非尼+曲美替尼疗效相当，且所有这些治疗方案在DFS方面均显著优于安慰剂。
考虑到疗效和耐受性，纳武单抗和帕博利珠单抗似乎是III-IV期黑色素瘤患者更合适的辅助治疗方案。对于BRAF突变阳性患者，仍需要更多的RCT来确定ICIs和靶向治疗哪种更好。
