Geparquinto: An interim safety analysis of epirubicin/cyclophosphamide followed by docetaxel with or without bevacizumab as neoadjuvant chemotherapy for primary breast cancer patients
Authors: G. Von Minckwitz, I. Bauerfeind, B. Gerber, H. Eidtmann, M. Kaufmann, S. D. Costa, S. Loibl, V. Nekljudova, M. Untch
Journal: Journal of Clinical Oncology (2009)

e11519^ Background: The GeparQuinto trial is investigating the incorporation of bevacizumab (B), RAD001 (everolimus) for HER2-negative, and lapatinib for HER2-positive patients (pts) into neoadjuvant treatment regimens. As these targeted agents have not yet been adequately tested in combination with epirubicin (E), cyclophosphamide (C), and docetaxel (T) chemotherapy, a run-in phase of the trial was conducted for safety reasons. Methods: Starting in 11/2007, 62 pts received 4 cycles of E: 90 mg/m 2 and C: 600 mg/m 2 , both on day 1 q day 21 followed by 4 cycles of T: 100 mg/m 2 , day 1 q day 21. Pts were randomized to receive this chemotherapy alone (EC-T, n=32) or concomitantly with B: 15 mg/kg i.v., day 1 q day 21 (ECB-TB, n=30). Main eligibility criteria for this part of the study were: histologically confirmed, HER2-negative, locally advanced breast cancer (cT3 cN+ and cT4), female, and ≥18 years of age with normal cardiac function (LVEF &gt;55%). This interim toxicity analysis was a prerequisite for opening the main phase of the HER2-negative trial part to also include pts with cT2 tumors. Results: 61 pts received all cycles of EC (n=31 EC-T, n=30 ECB-TB), 1 pt discontinued on investigator's decision, 1 pt discontinued after EC due to disease progression. 18 pts received all cycles of T in each of the EC-T and ECB-TB groups. Reasons for discontinuation of T were adverse events (n=2 EC-T, n=1 ECB-TB) or investigator's decision (n=1 EC-T). 17 pts completed all cycles of B. Statistically significant differences in toxicities were only observed for grade 3–4 leucopenia during EC (40.6%) and ECB (70.0%; p=0.024) and for grade 1–4 [grade 3–4] mucositis during T (52.4% [9.5%]) and TB (100% [36.8%]; p&lt;0.001 [p=0.060]). No statistically significantly different levels of other hematological or non-hematological toxicities were reported between the two arms. Conclusions: Addition of B to EC followed by T is feasible with the only increase in toxicity due to leucopenia and mucositis. Based on these data, the main phase of the trial was opened and has included over 450 pts to date. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .