F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070, Basel, Switzerland.
Centre Eugène Marquis, Rennes, France.
Breast Cancer Res Treat. 2020 Apr;180(3):597-609. doi: 10.1007/s10549-020-05577-7. Epub 2020 Feb 25.
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).
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.
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.
The efficacy and tolerability profiles of T-DM1 are generally favorable compared with other treatments for unresectable or metastatic HER2-positive BC.
由于缺乏头对头试验数据，我们采用网络荟萃分析（NMA）比较曲妥珠单抗-美坦新偶联物（T-DM1）与其他已获批用于治疗既往接受过不可切除或转移性人表皮生长因子受体 2（HER2）阳性乳腺癌（BC）且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患者的治疗方案。
检索 1998 年 1 月至 2018 年 1 月期间发表的关于不可切除或转移性 HER2 阳性 BC 患者辅助治疗后早期复发（≤6 个月）或Tras+紫杉烷治疗后进展的治疗方案的已发表对照试验的系统评价。采用随机效应 NMA 比较总生存期（OS）、无进展生存期（PFS）、总缓解率（ORR）和安全性结局。
NMA 纳入了来自 7 项随机对照试验的方案：T-DM1 与 Tras、卡培他滨（Cap）、拉帕替尼（Lap）、奈拉替尼（Ner）或帕妥珠单抗（Per；未获批）的联合方案。OS 结果显示 T-DM1 优于已获批的对照药物：风险比（HR）（95%可信区间[95%CrI]）分别为 Cap（0.68，0.39，1.10）、LapCap（0.76，0.51，1.07）、TrasCap（0.78，0.44，1.19）。PFS 趋势显示 T-DM1 优于其他所有治疗方法：HR（95%CrI）分别为 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 要好于所有已获批的治疗方法。在累积排序曲线下面积（SUCRA）分析中，T-DM1 在所有疗效结局中排名最高。与除奈拉替尼以外的所有对照药物相比，T-DM1 导致停药的可能性更低。一般来说，与对照药物相比，T-DM1 发生胃肠道副作用的可能性更低，发生肝转氨酶升高和血小板减少的可能性更高。
与其他用于治疗不可切除或转移性 HER2 阳性 BC 的治疗方案相比，T-DM1 的疗效和耐受性通常较好。
