Abstract P1-13-09: Prognostic relevance of prior endocrine treatments in overall survival (OS) at the time of first line chemotherapy in ER[+]/HER2[-] advanced breast cancer (ABC) patients
Authors: Llombart A , de la Haba-Rodríguez JR , Gligorov J , Aguirre E , Sampayo M , Cortes J 
Published: May 2016

Abstract
Background: International consensus stresses the preference for endocrine therapies (ET) for the ER[+]/HER2[-] ABC population. However, in real-world, chemotherapy (CT) is an extended practice long before exhausting endocrine options (Swallow E, Curr Med Res Opin. 2014). There is little knowledge on the prognostic factors that drives OS among the ER[+]/HER2[-] population at the time of first line CT for ABC.
Methods: The Athena trial assessed safety of different first-line CT & bevacizumab regimens in 2.264 patients (pts) treated between 2006 and 2009 over 34 countries. A total of 1.492 ER/PgR[+]/HER2[-] pts were identified, as 585 TNBC pts (control arm). We adapted the ESMO 2012 guidelines of endocrine resistance to the data collected, considering 5 years the median duration of (neo)adjuvant ET. Endocrine resistance status (ERS) at the time of inclusion was measured by: (1) Progression on ET for Early stage (EEP) [on or within the first year of], and (2) Prior ET for ABC (AEP), whatever the duration or number of endocrine lines. Three ES were pre-defined: Low sensitive (LS): patients with both EEP and AEP criteria; moderately sensitive (MS): either EEP or AEP criteria, and Highly sensitive (HS): neither EEP nor AEP criteria. Other prognostic factors (PF) identified in a prior analysis (Llombart-Cussac A, Breast 2014) were incorporated in a multivariate Cox proportional-hazard model.
Results: Median age was 53 years (range 22-93); 5.2% ECOG ≥2 and 28.9% with prior analgesic treatment. ER/PgR positivity were 94.4%/76% respectively. Patients were previously exposed to anthracycline (53.5%) and taxanes (21.4%) for early stage BC. Prior endocrine therapy in (neo)adjuvant and metastatic settings were (65.3%) and (31.8%), respectively. Pts de novo metastatic represented 19.3%, and the median DFI in pts progressing from an early stage was 43.2 mo. Liver involvement was observed in 40.3% of pts and 20.5% presented ≥3 organs involved. The ES for the population was HS: 492 pts (33%), MS: 755 pts (50.6%) and LS: 245 pts (16.4%). After median follow-up of 22.6 months (range: 0.1 to 43.6) and 752 OS events (50.4% of pts), median OS for HS, MS, LS and TNBC groups were &gt;40 mo. (median not achieved), 26.3 (95%CI: 24.5–28.4), 20.1 (95%CI: 17.8–23.9) and 18.3 (95%CI: 16.3–19.7) respectively. 3-years OS survival rates for HS, MS, LS and TNBC were 53.5%, 34.8%, 23.9% and 26.6%, respectively. Multivariate-adjusted hazard ratios of OS for (HS vs LS) and (HS vs MS) were 2 (IC95%: 1.6–2.5) and 1.5 (IC95%: 1.2–1.8). The other PF related with OS were: ECOG≥2 or analgesics or corticosteroids 1.6 (IC95%: 1.4–1.8); liver mets or&gt;2 involved organs 1.4 (IC95%: 1.2–1.6) and adjuvant anthracyline and/or taxane 1.2 (IC95%: 1.1–1.4).
Conclusions: Nearly to 40% of ER[+]/HER2[-] ABC pts confronted to first line CT were precluded as highly sensitive to ET, achieving a median OS that doubles the less sensitive groups. Confirmatory studies with post-treatment information may be important to link this benefit to ET. However Endocrine Status may be useful to appropriately characterize or select patients in future first-line CT studies for HER2[-] pts.
Citation Format: Llombart A, de la Haba-Rodríguez JR, Gligorov J, Aguirre E, Sampayo M, Cortes J. Prognostic relevance of prior endocrine treatments in overall survival (OS) at the time of first line chemotherapy in ER[+]/HER2[-] advanced breast cancer (ABC) patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-13-09.