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 and HER2- positive metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is non-inferior to trastuzumab plus chemotherapy.
We conducted an open-label, non-inferiority, phase-3, randomized, controlled trial (NCT01950182) at nine hospitals in China. Patients with HR+HER2+ MBC were enrolled. 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 non-inferiority upper margin of 1.35 for the hazard ratio. 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 (IQR 15.0-44.7), the median PFS was 19.2 months (95%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; pnon-inferiority <0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group.
Trastuzumab plus endocrine therapy was non-inferior to trastuzumab plus chemotherapy in patients with HR+HER2+ MBC.