Abstract OT1-14-02: Phase 3 study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09

Abstract

Abstract Background: A combination of a taxane, trastuzumab, and pertuzumab (THP) is the standard-of-care (SOC) 1L treatment for patients (pts) with HER2+ mBC; THP demonstrated median progression-free survival (mPFS) of 18.7 mo and overall survival (OS) of 56.5 mo (Swain et al. N Engl J Med. 2015;372:724-734). However, pts eventually develop resistance to treatment. Novel treatment options are necessary in order to delay the emergence of resistance and provide better clinical outcomes, improve quality of life (QOL), and prolong survival in the 1L setting. T-DXd has demonstrated efficacy in pts with heavily pretreated HER2+ mBC, with an objective response rate (ORR) of 61.4%, duration of response (DOR) of 20.8 mo, and mPFS of 19.4 mo (Modi et al. Cancer Res. 2021. Abstract PD3-06). Data from DESTINY-Breast01 supported global approvals of T-DXd in HER2+ mBC. Here we describe a phase 3 trial evaluating the efficacy and safety of T-DXd ± pertuzumab compared with THP in the 1L treatment of HER2+ mBC. Trial design: DESTINY-Breast09 (NCT04784715) is a global, multicenter, randomized, phase 3 trial assessing the efficacy and safety of T-DXd with or without pertuzumab compared with SOC THP as 1L treatment in pts with HER2+ (IHC 3+ or ISH+ assessed locally per ASCO-CAP guidelines and centrally confirmed) advanced or mBC. This study consists of 3 treatment arms: arm A (T-DXd + placebo), arm B (T-DXd + pertuzumab), and arm C (THP). Randomization is 1:1:1 and pts will be stratified by prior treatment status (de novo vs recurrent), hormone receptor status (positive vs negative), and PIK3CA mutation status (detected vs not detected). Pts (N≈1134) must have had no prior chemotherapy or HER2-targeted therapy for advanced or mBC (1 prior line of endocrine therapy is allowed for mBC). The primary endpoint is PFS by blinded independent central review. Secondary endpoints include PFS by investigator assessment, OS, ORR, DOR, PFS2, health-related quality of life (QOL), pharmacokinetics, immunogenicity, and safety. Citation Format: Sara M Tolaney, Romualdo Barroso-Sousa, Zefei Jiang, Yeon Hee Park, Mothaffar Rimawi, Cristina Saura, Andreas Schneeweiss, Masakazu Toi, Tinghui Yu, Jagdish Shetty, Pia Herbolsheimer, Sibylle Loibl. Phase 3 study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-14-02.