在ERBB2（前称HER2）阳性转移性乳腺癌（MBC）中，将曲妥珠单抗和帕妥珠单抗与以紫杉醇为基础的化疗联合应用是标准护理的一线治疗方案。鉴于曲妥珠单抗加帕妥珠单抗在ERBB2阳性MBC中已被证明有效，即使没有化疗，关于最佳的一线治疗策略是否可以仅为曲妥珠单抗加帕妥珠单抗而不使用化疗仍未解决。为评估随机分配至一线曲妥珠单抗加帕妥珠单抗单药治疗组或同时联合化疗后，发展后使用曲妥珠单抗和乳腊胺的患者的2年总生存和无进展生存；评估在曲妥珠单抗加帕妥珠单抗后的二线治疗中乳腊胺的无进展生存；评估ERBB2富集型和非富集型亚型的总生存和无进展生存。本研究是对一项在法国27个中心、瑞士20个中心、荷兰9个中心和德国1个中心进行的多中心、开放标签、2期随机临床试验的二次分析。总共有210名中央确认的ERBB2阳性的MBC患者在2013年5月3日至2016年1月4日期间进行随机分配，试验于2020年5月26日终止。数据分析时间为2020年12月18日至2022年5月10日。患者随机接受帕妥珠单抗（840 mg 静脉注射[IV]，然后每3周静脉注射420 mg IV）加曲妥珠单抗（8 mg/kg IV，然后每3周静脉注射6 mg/kg IV）而不使用化疗（A组）或帕妥珠单抗加曲妥珠单抗（相同剂量）与紫杉醇（90 mg/m2 持续4个月以上，每周1、8、15注射，然后每4周注射一次）或醋镁紫杉醇（第一次注射25 mg/m2，然后每3周在第1和第8天注射30 mg/m2，持续4个月以上）联合化疗，然后在化疗停用后继续接受帕妥珠单抗加曲妥珠单抗维持治疗（B组）。治疗组的总生存率（治疗组在24个月时），一线治疗的无进展生存，二线治疗的无进展生存和患者报告的生活质量（QOL）。共有210名患者纳入分析，中位年龄为58（范围，26-85）岁。对于A组，24个月总生存率为79.0%（90% CI，71.4%-85.4%）；对于B组，总生存率为78.1%（90% CI，70.4%-84.5%）。A组的一线治疗无进展生存中位时间为8.4个月（95% CI，7.9-12.0个月），B组为23.3个月（95% CI，18.9-33.1个月）。与预期不同，ERBB2富集型和非富集型癌症的总生存和无进展生存并没有明显的差异。没有化疗的不良事件较少，A组的生活质量相对基线有轻微改善，而B组的生活质量保持稳定。这项随机临床试验的二次分析结果表明，在总生存方面，不使用化疗的抗ERBB2策略是可行的而且不会对患者造成不良影响。基于50个基因预测分析微阵列签名，不能帮助确定此方法最适合的患者人群。ClinicalTrials.gov标识符：NCT01835236。

In ERBB2 (formerly HER2)-positive metastatic breast cancer (MBC), combining trastuzumab and pertuzumab with taxane-based chemotherapy is the first line of standard care. Given that trastuzumab plus pertuzumab was proven effective in ERBB2-positive MBC, even without chemotherapy, whether the optimal first-line strategy could be trastuzumab plus pertuzumab alone instead of with chemotherapy is unresolved.To assess overall survival (OS) at 2 years and progression-free survival (PFS) for patients randomly assigned to receive first-line pertuzumab plus trastuzumab alone or with chemotherapy followed by trastuzumab and emtansine at progression; PFS of second-line trastuzumab and emtansine treatment following trastuzumab plus pertuzumab; and OS and PFS in the ERBB2-enriched and ERBB2-nonenriched subtypes.This was a secondary analysis of a multicenter, open-label, phase 2 randomized clinical trial conducted at 27 sites in France, 20 sites in Switzerland, 9 sites in the Netherlands, and 1 site in Germany. Overall, 210 patients with centrally confirmed ERBB2-positive MBC were randomized between May 3, 2013, and January 4, 2016, with termination of the trial May 26, 2020. Data were analyzed from December 18, 2020, to May 10, 2022.Patients randomly received pertuzumab (840 mg intravenously [IV], then 420 mg IV every 3 weeks) plus trastuzumab (8 mg/kg IV, then 6 mg/kg IV every 3 weeks) without chemotherapy (group A) or pertuzumab plus trastuzumab (same doses) with either paclitaxel (90 mg/m2 for days 1, 8, and 15, then every 4 weeks for ≥4 months) or vinorelbine tartrate (25 mg/m2 for first administration followed by 30 mg/m2 on days 1 and 8 and every 3 weeks for ≥4 months) followed by pertuzumab plus trastuzumab maintenance after chemotherapy discontinuation (group B).Overall survival at 24 months by treatment group, PFS for first-line treatment, PFS for second-line treatment, and patient-reported quality of life (QOL).A total of 210 patients were included in the analysis, with a median age of 58 (range, 26-85) years. For group A, 24-month OS was 79.0% (90% CI, 71.4%-85.4%); for group B, 78.1% (90% CI, 70.4%-84.5%). Median PFS with first-line treatment was 8.4 (95% CI, 7.9-12.0) months in group A and 23.3 (95% CI, 18.9-33.1) months in group B. Unlike expectations, OS and PFS did not markedly differ between populations with ERBB2-enriched and ERBB2-nonenriched cancer. Adverse events were less common without chemotherapy, with small QOL improvements from baseline in group A and stable QOL in group B.The findings of this secondary analysis of a randomized clinical trial suggest that the chemotherapy-free anti-ERBB2 strategy is feasible without being detrimental in terms of OS. The 50-gene prediction analysis of microarray signature could not help to identify the most appropriate patient population for this approach.ClinicalTrials.gov Identifier: NCT01835236.