Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Clin Cancer Res. 2022 Feb 15;28(4):637-645. doi: 10.1158/1078-0432.CCR-21-3435.
There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy.
We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses.
A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n = 196) or trastuzumab plus chemotherapy (CT group, n = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0-44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7-21.7)] in the ET group and 14.8 months (12.8-16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71-1.09; Pnoninferiority < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group.
Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR+HER2+ MBC.
目前尚无研究证据表明，在激素受体（HR）阳性（HR+）和人表皮生长因子受体 2 阳性（HER2+）转移性乳腺癌（MBC）的一线治疗中，内分泌治疗与化疗联合应用作为抗 HER2 治疗的哪种联合策略更好。我们希望确定曲妥珠单抗联合内分泌治疗是否不劣于曲妥珠单抗联合化疗。
我们在中国的 9 家医院进行了一项开放标签、非劣效性、III 期、随机、对照试验（NCT01950182）。根据既往辅助内分泌治疗和疾病状态（复发 vs. 初发转移），将参与者分层，按 1:1 随机分配接受曲妥珠单抗联合内分泌治疗（研究者选择雌激素受体调节剂或芳香化酶抑制剂，联合或不联合卵巢抑制）或化疗（研究者选择紫杉类、卡培他滨或长春瑞滨）。主要终点是无进展生存期（PFS），HR 的非劣效性上限为 1.35。主要和安全性分析采用意向治疗人群。
共纳入 392 例患者并按随机分组接受曲妥珠单抗联合内分泌治疗（ET 组，n=196）或曲妥珠单抗联合化疗（CT 组，n=196）。中位随访 30.2 个月[四分位距（IQR）15.0-44.7]后，ET 组中位 PFS 为 19.2 个月[95%置信区间（CI），16.7-21.7]，CT 组为 14.8 个月（12.8-16.8）（风险比，0.88；95%CI，0.71-1.09；P非劣效性<0.0001）。与 ET 组相比，CT 组毒性反应发生率明显更高。
在 HR+HER2+MBC 患者中，曲妥珠单抗联合内分泌治疗不劣于曲妥珠单抗联合化疗。
