背景：對於激素受體陽性和 HER2 陽性的轉移性乳腺癌，在抗 HER2 治療加內分泌治療，或者抗 HER2 治療加化療，兩種方案中沒有證據表明哪種一線方案為首選。本研究的目的是確定曲妥珠單抗聯合內分泌治療是否與曲妥珠單抗聯合化療一樣有效，並降低毒性作用。

Background: For metastatic breast cancer with hormone receptor-positive and HER2-positive, no evidence showed that which first-line regimens were preferred, either anti-HER2 therapy plus endocrine therapy or anti-HER2 therapy plus chemotherapy. This study aimed to determine whether trastuzumab plus endocrine therapy is as efficacious as trastuzumab plus chemotherapy and with decreased toxic effects.

方法：我們在中國 9 家醫院進行了一項開放性、非劣效性、3 期、隨機、對照試驗。組織學證實的激素受體陽性和 HER2 陽性的晚期乳腺癌患者隨機分為 1：1 組接受曲妥珠單抗聯合化療（CT組）或內分泌治療（ET 組）。主要終點是無進展生存率，危險比（HR）的非劣效性上界為 1.35。

Methods: We conducted an open-label, non-inferiority, phase 3, randomized, controlled trial at nine hospitals in China. Patients with hormone receptor-positive and HER2-positive histologically confirmed advanced breast cancer were randomly assigned (1:1) to receive trastuzumab plus chemotherapy (CT group) or endocrine therapy (ET group). The primary endpoint was progression-free survival with a non-inferiority upper margin of 1.35 for the hazard ratio (HR).

結果：在 2013 年 9 月 16 日至 2019 年 12 月 28 日期間，共有 392 名患者入組被隨機分配接受曲妥珠單抗加內分泌治療（n=196）或曲妥珠單抗加化療（n=196）。在意向治療人群中，CT 組 PFS中位數為 14.8 個月（95%CI12.8-16.8），ET 組 PFS 中位數為 19.2 個月（95%CI16.7-21.7）（HR0.88，95%CI 0.71-1.09；P 非劣效性＜0.0001）。與 ET 組相比，CT 組的毒性發生率明顯增高，包括白細胞減少（98[50%]vs13[6.6%]）、惡心（93[47%]vs24[12%]）、疲勞（47[24%]vs31[16%]）、嘔吐（45[23%]vs12[6%]）、頭痛（65[33%]vs24[12%]）和脫發（125[64%]vs8[4%]）。沒有患者死於治療相關的原因。

Results: Between Sep 16, 2013, and Dec 28, 2019, 392 patients were enrolled and randomly assigned to receive trastuzumab plus endocrine therapy (n = 196) or trastuzumab plus chemotherapy (n = 196). In the intention-to-treat population, the median PFS was 14.8 months (95% CI 12.8-16.8) in the CT group and 19.2 months (95% CI 16.7-21.7) in the ET group (HR 0.88, 95% CI 0.71-1.09; Pnon-inferiority< 0.0001). Significantly higher frequency of toxicities were observed in CT group compared with ET group, including: leucopenia (98 [50%] vs 13 [6.6%]), nausea (93 [47%] vs 24 [12%]), fatigue (47 [24%] vs 31 [16%]), vomiting (45 [23%] vs 12 [6%]), headache (65 [33%] vs 24 [12%]) and alopecia (125 [64%] vs 8 [4%]). No patients died from treatment-related causes.

結論：對激素受體陽性和 HER2 陽性的轉移性乳腺癌患者，曲妥珠單抗聯合內分泌治療不劣於曲妥珠單抗聯合化療，且毒副作用降低。曲妥珠單抗聯合內分泌治療可以提供更方便的治療，並且治療耐受性更好。

Conclusions: Trastuzumab plus endocrine therapy was non-inferior to and had decreased toxicities to trastuzumab plus chemotherapy in patients with metastatic breast cancer with hormone receptor-positive and HER2-positive. Trastuzumab plus endocrine therapy could provide more convenient treatment and allow better treatment tolerance.