Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment 1 for Patients with Metastatic Breast Cancer with Hormone Receptor-positive and 2 HER2-positive (SYSUCC-002)

first-line therapy patients HR+HER2+ therapy Abstract 70 Purpose: There is no research evidence demonstrate which is the better partner 71 strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as 72 the first line management of hormone receptor (HR)-positive and HER2- positive 73 metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine 74 therapy is non-inferior to trastuzumab plus chemotherapy. 75 Experimental Design: We conducted an open-label, non-inferiority, phase-3, 76 randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, 77 stratified by previous adjuvant endocrine therapy and disease status (recurrent disease 78 vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus 79 endocrine therapy (per investigator's choice of oestrogen-receptor modulators or 80 aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy 81 (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary 82 endpoint was progression-free survival (PFS) with a non-inferiority upper margin of 83 1.35 for the hazard ratio. The intention-to-treat population was used in primary and 84 safety analyses. Results: A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n=196) or trastuzumab plus 87 chemotherapy (CT group, n=196). After a median follow-up of 30.2 months (IQR 88 15.0–44.7), the median PFS was 19.2 months (95%CI 16.7–21.7) in the ET group and 89 14.8 months (12.8–16.8) in the CT group (hazard ratio 0.88, 95%CI 0.71–1.09; p non-inferiority <0.0001). A significantly higher prevalence of toxicity was observed in