Abstract P5-19-26: Efficacy and tolerance of everolimus in 123 consecutive very advanced luminal breast cancer patients. A multicenter retrospective study
Authors: Chocteau-Bouju Dorothée , Chakiba Camille , Mignot Laurent , Madranges Nicolas , Pierga Jean-Yves , Beuzeboc Philippe , Quenel-Tueux Nathalie , Diéras Véronique , Bonnefoi Hervé , Debled Marc , Cottu Paul H 
Published: May 2015

Abstract
Background: The on line publication in December 2011 of the Bolero-2 study (Baselga et al, NEJM) establishing the added value of everolimus (Eve) in endocrine resistant breast cancer (BC) patients (pts) has triggered its immediate use in current practice. We evaluated our practice 2 years (y) after the French marketing authorization (July 2012).
Patients and Methods: We retrospectively reviewed the medical charts of 123 consecutively treated pts in two Unicancer Institutions (Institut Curie & Institut Bergonié). All pts had luminal (ER positive, HER2 negative) BC. Median age at diagnosis was 48 y (29-78) and median delays to first met event and to everolimus therapy were 6.0 y (0-25) and 12.6 y (1.3-34.8), respectively. PS at inclusion was 0 (47.6%), 1 (50.8%) or 2 (1.6%). Pts had received a median number of 2 lines of chemotherapy (0-8) and of 2 lines of endocrine therapy (0-6) for metastatic disease. Visceral disease was present in 56% of the pts. Pts had either 1 (25.4%), 2 (32.2%) or 3+ (42.4%) involved sites.
Results: Eve based therapy. Initial dose of Eve was 10 mg (76.4%) or 5 mg (23.6%) and was combined with exemestane (79.9%), anastrozole/letrozole (14.0%) or tamoxifen (6.1%). GnRH agonists were used in 10 premenopausal women. Dose adjustments of Eve were necessary in 41.7% of the 10 mg pts, and in 33.3% of the 5 mg pts (p=0.426). Overall, grade 2 or grade 3 side effects were experienced by 47.7% and 34% of the pts, respectively. Most frequent side effects were grade 2/3 mucositis (32.5%/11.2%), grade 1/2 decreased appetite (42.8%/24.3%), grade 1/2 rash (46.7%/22.7%), and grade 2/3 fatigue (33.3%/7.1%). Grade 2/3 weight loss was observed in 27.2%/7.6% of the pts. Only 5 cases of grade 3 pneumonitis were recorded. One patient had a grade 4 hypercholesterolemia which quickly resolved after cessation of therapy. No toxicity related death was observed.
Response and Survival. Out of 116 evaluable/measurable pts, the best observed response was disease improvement (RECIST and non RECIST objective response) in 47 pts (40.5%), stable disease in 28 pts (24.1%) and progressive disease in 41 pts (35.4%). From onset of Eve based therapy and after a median follow up of 10 mo, overall survival was 21 mo (0.4-26+), median progression free survival was 9 mo (0.4-26+), and time to treatment failure was 5.7 mo (0.4-16+). Eve was stopped for progression, toxicity or both in 64 pts (52%), 36 pts (29.2%) and 8 pts (6.5%) respectively. Multivariate analysis showed that more than 2 lines of previous chemotherapy was an independent predictor for PFS (HR for progression=2.28 – p=0.01), and that 2 or more involved sites was an independent predictor for OS (HR for death=2.7 – p=0.021).
Conclusion: We evaluated a multicenter population in routine practice of very advanced, slowly evolving luminal BC patients, which appears very close to the Bolero-2 population although more heavily pretreated. Eve based therapy appears feasible with dose reduction in more than 40% of the population and side effect rates are very similar to those reported in the pivotal Bolero-2 trial. Efficacy is highly encouraging and deserves a further evaluation of everolimus in this population.
Citation Format: Dorothée Chocteau-Bouju, Camille Chakiba, Laurent Mignot, Nicolas Madranges, Jean-Yves Pierga, Philippe Beuzeboc, Nathalie Quenel-Tueux, Véronique Diéras, Hervé Bonnefoi, Marc Debled, Paul H Cottu. Efficacy and tolerance of everolimus in 123 consecutive very advanced luminal breast cancer patients. A multicenter retrospective study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-26.