Abstract S5-03: Final analysis of WSG-ADAPT HER2+/HR+ phase II trial: Efficacy, safety, and predictive markers for 12-weeks of neoadjuvant TDM1 with or without endocrine therapy versus trastuzumab+endocrine therapy in HER2-positive hormone-receptor-positive early breast cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-02, Vol.76 (4_Supplement), p.S5-S5-03
• Main Authors: Harbeck, N, Gluz, O, Christgen, M, Braun, M, Kuemmel, S, Schumacher, C, Potenberg, J, Kraemer, S, Kleine-Tebbe, A, Augustin, D, Aktas, B, Forstbauer, H, Tio, J, Liedtke, C, Kates, RE, Wuerstlein, R, de Haas, SL, Kiermaier, A, Kreipe, HH, Nitz, U
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.SABCS15-S5-03

Background: In HER2+ early breast cancer (eBC) pCR rates after standard neoadjuvant chemo- + anti-HER2 therapy differ according to hormone-receptor (HR) status. Molecular analysis reveals HER2+/HR+ BC as a distinct entity within HER2+ BC. The ADAPT HER2+/HR+ phase II trial aims to identify early responders to endocrine + anti-HER2 therapy. Methods: The trial completed recruitment in January 2015 (n=376). Patients (pts.) were randomized to 12 weeks of neoadjuvant therapy: A:T-DM1 (3.6 mg/kg q3w) vs. B:T-DM1 with endocrine therapy (ET) (pre-: tamoxifen; postmenopausal: aromatase inhibitor) vs C:trastuzumab q3w+ET. After surgery, standard chemotherapy at investigators' discretion and completion of 1y trastuzumab were recommended. Trial tests pCR (yPN0 and ypT0/is) in after T-DM1 or T-DM1+ET compared to T+ET. Biomarkers are measured at baseline and after 3 weeks. Results: Pre-planned interim analysis (n=130) aimed to identify an early-response biomarker (e.g. Ki-67 drop) and to validate trial assumptions. Median age was 49 years; 55% were pre-menopausal; 40% had cT1 tumors, 51% cT2; 68% had cN0, 27% cN1; 75% had G3. Median baseline Ki67 was 30%. In all arms, more than 95% received all 4 therapy cycles. 16 SAEs were reported in 13 pts (A:7; B:6; C:3); all CTC grade 1 (1), 2 (11) or 3 (4); all pts completely recovered without sequelae. Overall pCR rate was 30.8%: T-DM1: 40.5%, T-DM1+ET: 45.8%, T+ET: 6.7%. The difference between either arm T-DM1 arm vs. T+ET was significant (p