147649-156

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.

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

506

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 506)
Author(s): 
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

Abstract: 

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