PURPOSE In the absence of head-to-head trial data, network meta-analysis (NMA) was used to compare trastuzumab emtansine (T-DM1) with other approved treatments for previously treated patients with unresectable or metastatic HER2-positive breast cancer (BC). METHODS Systematic reviews were conducted of published controlled trials of treatments for unresectable or metastatic HER2-positive BC with early relapse (≤ 6 months) following adjuvant therapy or progression after trastuzumab (Tras) + taxane published from January 1998 to January 2018. Random-effects NMA was conducted for overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety endpoints. RESULTS The NMA included regimens from seven randomized controlled trials: T-DM1 and combinations of Tras, capecitabine (Cap), lapatinib (Lap), neratinib, or pertuzumab (Per; unapproved). OS results favored T-DM1 over approved comparators: hazard ratio (HR) (95% credible interval [95% CrI]) vs Cap 0.68 (0.39, 1.10), LapCap 0.76 (0.51, 1.07), TrasCap 0.78 (0.44, 1.19). PFS trends favored T-DM1 over all other treatments: HR (95% CrI) vs Cap 0.38 (0.19, 0.74), LapCap 0.65 (0.40, 1.10), TrasCap 0.62 (0.34, 1.18); ORR with T-DM1 was more favorable than with all approved treatments. In surface under cumulative ranking curve (SUCRA) analysis T-DM1 ranked highest for all efficacy outcomes. Discontinuation due to adverse events was less likely with T-DM1 than with all comparators except neratinib. In general, gastrointestinal side effects were less likely and elevated liver transaminases and thrombocytopenia more likely with T-DM1 than with comparators. CONCLUSIONS The efficacy and tolerability profiles of T-DM1 are generally favorable compared with other treatments for unresectable or metastatic HER2-positive BC.

中文翻译：

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评估既往接受过治疗、不可切除或转移性 HER2 阳性乳腺癌患者接受紫杉烷/曲妥珠单抗治疗后各种 HER2 靶向治疗方案的临床有效性和安全性：系统评价和网络荟萃分析。


目的 在缺乏头对头试验数据的情况下，使用网络荟萃分析 (NMA) 将曲妥珠单抗 emtansine (T-DM1) 与其他批准的治疗方法用于既往接受过治疗的不可切除或转移性 HER2 阳性乳腺癌 (BC) 患者的比较）。方法 对 1998 年 1 月至 2018 年 1 月发表的辅助治疗后早期复发（≤ 6 个月）或曲妥珠单抗 (Tras) + 紫杉烷治疗后进展的不可切除或转移性 HER2 阳性 BC 治疗的对照试验进行了系统评价。 随机效应NMA 的目的是评估总生存期 (OS)、无进展生存期 (PFS)、总缓解率 (ORR) 和安全性终点。结果 NMA 包括来自七项随机对照试验的治疗方案：T-DM1 以及 Tras、卡培他滨 (Cap)、拉帕替尼 (Lap)、来拉替尼或帕妥珠单抗（Per；未批准）的组合。与批准的比较器相比，T-DM1 的 OS 结果更有利：风险比 (HR)（95% 可信区间 [95% CrI]）对比 Cap 0.68 (0.39, 1.10)、LapCap 0.76 (0.51, 1.07)、TrasCap 0.78 (0.44, 1.19) 。 PFS 趋势优于所有其他治疗：HR (95% CrI) 对比 Cap 0.38 (0.19, 0.74)、LapCap 0.65 (0.40, 1.10)、TrasCap 0.62 (0.34, 1.18)； T-DM1 的 ORR 比所有已批准的治疗方法更有利。在累积排名曲线下表面 (SUCRA) 分析中，T-DM1 在所有疗效结果中排名最高。与除来那替尼外的所有比较药物相比，T-DM1 因不良事件而停药的可能性较小。一般来说，与对照组相比，T-DM1 出现胃肠道副作用的可能性较小，并且肝转氨酶升高和血小板减少的可能性更大。 结论 对于不可切除或转移性 HER2 阳性 BC，T-DM1 的疗效和耐受性总体上优于其他治疗方法。