Efficacy of 12-weeks of neoadjuvant TDM1 with or without endocrine therapy in HER2-positive hormone-receptor-positive early breast cancer: WSG-ADAPT HER2+/HR+ phase II trial.

Breast Cancer—HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer—HER2/ER
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 506)
Nadia Harbeck, Oleg Gluz, Matthias Christgen, Michael Wilhelm Braun, Sherko Kummel, Jochem Potenberg, Bahriye Aktas, Claudia Schumacher, Helmut Forstbauer, Doris Augustin, Stefan Kraemer, Marianne Just, Joke Tio, Anke Kleine-Tebbe, Cornelia Liedtke, Ronald E. Kates, Daniel Hofmann, Rachel Wuerstlein, Hans Heinrich Kreipe, Ulrike Nitz, West German Study Group ADAPT HER2+/HR+ Investigators; University of Munich, Otterfing, Germany; West German Study Group, Moenchengladbach, Germany; Hannover Medical School, Hannover, Germany; Rotkreuzklinikum, Munich, Germany; Kliniken Essen-Mitte (KEM), Essen, Germany; Department of Hematology, Waldkrankenhaus Spandau, Berlin, Germany; University Hospital Essen, Essen, Germany; St. Elisabeth Hospital, Köln, Germany; Praxisnetzwerk Hämatologie / intern. Onkologie, Troisdorf, Germany; Klinikum Deggendorf, Deggendorf, Germany; Department of Obstetrics & Gynecology, University Hospital of Cologne, Cologne, Germany; Oncologic Practice Bielefeld, Bielefeld, Germany; University Clinics Münster, Münster, Germany; DRK Kliniken Berlin Köpenick, Berlin, Germany; University of Schleswig-Holstein Campus Luebeck, Luebeck, Germany; REK Consulting, Otterfing, Germany; University of Munich, Munich, Germany; Geriatric Breast Center, Evangelina Bethesda Hospital for Breast Diseases, Nordrhein-Westfalen, Germany

Abstract Disclosures


Background: Evidence suggests differential efficacy of standard neoadjuvant chemo- + targeted therapy in HER2+ early breast cancer (eBC) according to hormone-receptor (HR) status. ADAPT HER2+/HR+ aims to identify responders to dual targeted therapy, which has not been widely explored. Methods: 380 patients (pts) receive 12 weeks of neoadjuvant therapy. Arms A/B: T-DM1 (3.6 mg/kg q3w) ± endocrine therapy (ET) (pre-: tamoxifen; postmenopausal: aromatase inhibitor); Arm C (control): q3w trastuzumab + ET. After surgery, pts are to receive 4xEC – 12xpaclitaxel weekly (investigators’ discretion) and complete 1y trastuzumab. Trial tests pCR (yPN0 and ypT0/is) in Arms A and B compared to control (C). 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, 95-100% received all 4 therapy cycles. 15 SAEs occurred in 12 pts (A:4; B:6; C:2), majority are CTC grades 2 (9) or 3 (4); all pts completely recovered without sequelae. Overall pCR rate was 30.8%: A: 40.5%, B: 45.8%, C: 6.7%. The difference between either arm A or B vs. C was significant (p < 0.001), but not A vs. B. Exploratory analysis suggests benefit of adding ET to T-DM1 in pre- (pCR: 28.6% for T-DM1 single agent vs. 47.6% with ET) but not in postmenopausal pts (pCR: 64.3% vs. 50%). Ki-67 quantification in the 3-week biopsy was not possible in 43.1%, mostly due to low tumor cell counts ( < 500); of the remaining tumors, 21.6% (16/74) had Ki-67 ≤ 10% after first cycle. Final data set is required to substantiate these findings which may also be impacted by the different ET options (Tam vs. AI). Conclusions: The interim analysis demonstrates for the first time clinically meaningful pCR rates ( > 40%) after only 12 weeks of T-DM1 ± ET without systemic chemotherapy in HER2+/HR+ eBC. Ongoing biomarker analyses include PI3K mutations and intrinsic subtypes. In 1/2015, registration phase was completed at 449 pts. Clinical trial information: NCT01745965