Maintenance with everolimus (RAD001) and trastuzumab (T) after discontinuation of chemotherapy in patients (pts) with heavily pretreated HER2-positive metastatic breast cancer (MBC): Pooled data of extension cohorts of phase Ib/II studies.
Authors: G. H. Jerusalem, A. Fasolo, C. Massacesi, M. Balaisius, C. Manlius, T. Sahmoud, F. Andre, L. Gianni
Journal: Journal of Clinical Oncology (2010)

1041^ Background: Continuing treatment with T after discontinuation of chemotherapy is commonly used as an approach aiming to delay disease progression. The aim of this descriptive analysis is to evaluate the safety and efficacy of the combination of RAD001 + T after pts have discontinued the planned chemotherapy. Methods: Data from two multicenter Novartis-sponsored phase I/II studies (NCT00426556 and NTC00426530), with a comparable study design and patient population, were pooled. Regimens were: oral RAD001 daily (5 or 10mg) or weekly (20 or 30mg); weekly T 2mg/kg IV; paclitaxel (P) 80mg/m2, IV D1-8-15 q4w (88 pts enrolled) or vinorelbine (V) 25 mg/m2, IV D1-8 q3w (50 pts). After a core phase in which the pts received 6 cycles of RAD, T, and either P or V, the pts were allowed to enter an extension phase in which the cytotoxic drug could be discontinued. Results: As of November 30, 2009 (cut-off date), 30/138 pts (22%) continued RAD001 + T after discontinuation of chemotherapy. All pts were heavily pretreated, trastuzumab-resistant and taxane-pretreated. The median duration of treatment prior to discontinuation of chemotherapy was 23 wks (range 10-39). In the extension phase, 8/30 pts were still on treatment, RAD001 + T median treatment duration was 16 wks (range 1-82) after discontinuation of chemotherapy. During the chemotherapy phase, the best response was CR in 4 pts (13%), PR in 10 pts (33%) and SD in the remaining 16 pts (53%). One additional complete response occurred during the extension phase. Overall median PFS was 42 weeks (range 23-105), with a median value of 17 weeks (range 2-83) in the extension phase. In the extension phase the treatment was well-tolerated. The most common severe AEs were: G3/4 neutropenia in 4 pts (13%), G3 lymphopenia in 2 pts (7%), G3 asthenia in 2 pts (7%), and G3 weight loss in 2 pts (7%). Conclusions: Maintenance of RAD001 + T after chemotherapy appears to be a safe and effective approach to prolong PFS in heavily pretreated HER2-positive MBC patients. Updated results will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Genentech, GlaxoSmithKline, Novartis, Pfizer, Roche, Wyeth Novartis Novartis Novartis 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 2010 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.