Abstract P1-18-19: Long term results with everolimus in advanced hormone receptor positive breast cancer in a multicenter national real world observational study (ESME)
Authors: Francois-Martin Hélène , Lardy-Cleaud Audrey , Pistilli Barbara , Levy Christelle , Diéras Véronique , Frenel Jean-Sébastien , Guiu Séverine , Mouret-Reynier Marie-Ange , Mailliez Audrey , Eymard Jean-Christophe , Petit Thierry , Ung Mony , Desmoulins Isabelle , Augereau Paule , Bachelot Thomas , Uwer Lionel , Debled Marc , Ferrero Jean-Marc , Veyret Corinne , Goncalves Antony , Chevrot Michael , Cottu Paul H 
Published: March 2022

Abstract
Background The everolimus (EVE)-exemestane combination has been included in the International guidelines for metastatic HR+/HER2- breast cancer (mBC) since the results of the Bolero-2 trial. Marketing authorization has been granted in France in July 2012. A first report of the UNICANCER Epidemiological Strategy and Medical Economics (ESME) Research program described the real world use of everolimus therapy (ESMO 2017, #266). We report here updated data with long-term overall survival (OS) analyses, focusing on patients treated from 2012 onwards. Methods All patients (pts) who initiated treatment for a newly diagnosed mBC between 2008 and 2017 in all 18 French Comprehensive Cancer Centers have been included in the real life ESME database, which collects retrospective data using a clinical trial-like methodology. The primary endpoint of the present report was overall survival in pts who received everolimus. In order to adjust for differences between groups (EVE treated vs non EVE treated patients), we analyzed the impact of everolimus on OS and PFS by using a propensity score and inverse probability of treatment weighting (IPTW) sensitivity analyses, built with relevant cancer-related clinical variables in relation to survival and allocation of treatment. Those analyses were performed by line 1, 2 or 3 of treatment for mBC. Results The ESME program included 23,698 pts of whom 1897 with HR+/HER2- mBC received at least 1 dose of EVE and were diagnosed after 2012. Median age was 63 y (22-103). EVE pts were slightly younger than non-EVE pts (25.9% and 23.7% under 52 y, respectively, p=0.0574). EVE treated pts had more frequent non visceral metastases (52.3% vs 47.9%) and bone only metastases (38.5% vs 31.3%) at metastatic diagnosis, and less symptoms at mBC diagnosis (42.4% vs 47.5%) than non-EVE pts (all p values &lt;.001). 94.3% of EVE pts had received an EVE-exemestane combination. EVE was administered either in the 1st, 2nd or 3rd line+ setting, in 3.3%, 14.7% and 25.3% of all cases respectively. At each line, treatments in the non-EVE treated pts included various endocrine therapy or chemotherapy regimen. Median follow-up was 47.9 m (0-98.7), and 61.4 m (2.1-98.7) for the overall- and EVE treated populations, respectively. Crude and landmark (6 and 12 months) OS analyses all suggested a longer OS with EVE based therapy. IPTW analyses by lines of treatment, comparing EVE-treated and non-EVE-treated patients, suggested a longer progression free survival with EVE when administered in the 3rd line setting (HR=0.82 CI95% [0.745-0.903], p&lt;.0001). IPTW analyses consistently showed a significantly longer OS with EVE based treatment when administered in lines 1, 2 and 3 with respective HR values of 0.34, 0.34 and 0.23 (Table). Causes for EVE discontinuation were mainly disease progression (54%) and toxicity (26.6%). An exploratory analysis showed that 998 EVE treated patients (52.6%) also received a CDK4/6 inhibitor based treatment, mostly after EVE therapy (n=826, 82.8%). Median duration of CDK4/6 inhibitor therapy for those patients was 4.6 months (IQR 2.9-8.7). Conclusions These results are limited by the retrospective nature of the study and the lack of performance status, comorbidity or nutritional data. However, the long-term follow up of the ESME database suggests a favorable association between everolimus therapy and overall survival in HR+, HER2- mBC, persistent after IPTW adjusted analyses.
HR (CI95%)p value12 months OS EVE vs not (unadjusted Kaplan Meier)Line 10.34 (0.16-072).005497% vs 93%Line 20.34 (0.22-0.52)&lt;.000194% vs 85%Line 30.23 (0.14-0.36)&lt;.000195% vs 79%
Citation Format: Hélène Francois-Martin, Audrey Lardy-Cleaud, Barbara Pistilli, Christelle Levy, Véronique Diéras, Jean-Sébastien Frenel, Séverine Guiu, Marie-Ange Mouret-Reynier, Audrey Mailliez, Jean-Christophe Eymard, Thierry Petit, Mony Ung, Isabelle Desmoulins, Paule Augereau, Thomas Bachelot, Lionel Uwer, Marc Debled, Jean-Marc Ferrero, Corinne Veyret, Antony Goncalves, Michael Chevrot, Paul H Cottu. Long term results with everolimus in advanced hormone receptor positive breast cancer in a multicenter national real world observational study (ESME) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-19.