P5-22-01: Feasibility and Patient Safety of Serial Biopsies (bx) in Metastatic HER2−Positive Breast Cancer (BC) To Evaluate Alterations in Molecular Biomarkers (BM): Preliminary Results of SHERsig (Study of HER2 Signature in Metastatic Breast Cancer) a Prospective Phase II Study.

Abstract

Abstract Background The use of trastuzumab (H)-based therapy for HER2−positive BC has significantly altered outcomes. Yet up to 64% of metastatic patients (pts) fail to respond (Robert JCO 2006) and most pts will progress within 24–42 months (m) following an initial response for metastatic disease. Preclinical data suggest several in vitro resistance mechanisms but confirmatory in vivo data are lacking, preventing optimal personalized care. This ongoing proof-of-concept study examines serial bx in pts with HER2−positive metastatic BC in order to assess BM profiles across multiple lines of treatment. Methods: Key eligibility criteria include: centrally confirmed HER2 status, minimum of 1 disease site considered suitable for serial bx, normal coagulation profile and cardiac function, prior adjuvant/neoadjuvant taxane and H completed ≥12 m and ≥6 m respectively, ECOG ≤2. Pts receive q3wk H with clinician choice of taxane (docetaxel 75–100 mg/m2 q21, paclitaxel 80 mg/m2 weekly or 175 mg/m2 q21 [TH]). At the time of progressive disease, pts receive capecitabine (X) and H. Two core bx and 1 optional fine needle aspirate are performed at the following times: baseline (after 3 weeks [w] of TH), at 6 w, at time of first progression prior to XH, and at the time of progression on XH. Tumor assessments are performed at 6 w, then 9 w intervals, with cardiac assessment every 6 m. Primary endpoint aims to explore and potentially define BM signatures that could alter during HER2−targeted therapy and predict for decreased or increased sensitivity to H-based treatment. Secondary endpoints include bx safety, ORR and TTP. At time of baseline bx, pts have the option to complete a pt satisfaction questionnaire. Results: Between August 2009 and June 2011, 58 pts were screened; 29 enrolled. The other 29 pts were screen failures, with 3 pts (5%) specifically declining entry due to the requirement for serial bx. Median age is 53 y (range 37–86), with 9 and 20 pts having recurrent or de novo metastatic disease. Eight pts received adjuvant systemic treatment, including H in 4 pts. Baseline bx performed in the breast, n (%): 15 (52), bone: 6 (21), liver: 4 (14), and lymph nodes: 4 (14); 14 and 27 pts underwent bx at 3 and 6 w respectively. After a median of 34 w of treatment 11 pts progressed on TH and 7 pts underwent planned bx. There were 12 SAEs, none related to bx. Most AEs were grade 1/2 (95%) with 3% grade 3 and 1 death due to intercurrent illness. From a total of 43 bx, 12 (27%) grade 1/2 AEs (hematoma 2, transient hypotension 2, mild pain 8) were reported, with resolution in all instances. Fifteen pts consented to the pt satisfaction substudy. Conclusions: Preliminary results of the first reported serial bx study in metastatic BC demonstrated 95% pt acceptance of this approach. Evaluation of BM profiles will be conducted following planned recruitment of 50 pts. To date, the feasibility and safety of obtaining serial bx in metastatic BC is supported by the current safety profile and patient uptake. Updated recruitment data will be presented. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-22-01.