Abstract P2-08-10: Time-evolution of the efficacy of first line aromatase inhibitors (AI) in hormone receptor positive (HR+) advanced breast cancer (ABC): A moving target

Abstract

Abstract INTRODUCTION. Recently presented studies suggest significant improvements in efficacy of endocrine therapy trials addressing HR+ ABC. Overall, progression-free survival (PFS) has consistently improved when we analyze first line endocrine trials. This study aims to evaluate the evolution of the PFS obtained with first line AI monotherapy in patients with HR+ ABC. METHODS. We performed a systematic review of the literature searching for randomized clinical trials of endocrine therapy in HR+ ABC. All trials published since 2000 that involved a first line AI single agent arm were included. Median PFS, year of publication, sample size and population characteristics such as previous endocrine therapy exposure and presence of visceral metastases were extracted from each study and linear correlation used to access the trend of PFS along time. RESULTS. 13 studies were identified accounting for 3,446 postmenopausal patients that received monotherapy with an AI as first line treatment for HR+ ABC. The year of publication/presentation ranged from 2000 to 2016. A total of 14 treatment arms exploring AI monotherapy were identified and analyzed. One study compared exemestane to anastrozole. The other 12 studies compared AIs as single agents to other endocrine strategies. Single agent anastrozole was used in six studies while letrozole was used in five and exemestane in one trial. PFS ranged from 8.2 months in the experimental arm treated with anastrozole in a trial published in 2000 to 15.6 in the control group treated with letrozole monotherapy in a study published in 2015. Linear regression showed a significant improvement in PFS over time (p = 0.034). Table 1: studies characteristicsFIRST AUTHORAIYEAR OF PUBLICATIONPHASENPFS (m)HT NAIVE POP (%)VISCERAL METS (%)BONETTEREANASTROZOLE200033408.28833NABHOLTZANASTROZOLE2000317111.18047MOURIDSENLETROZOLE200134539.48145PARIDAENSEXEMESTANE200831829.99047ROBERTSONANASTROZOLE2010210313.17551MEHTAANASTROZOLE2012334513.56049BERGHANASTROZOLE2012325610.23351MARTINLETROZOLE2012316614.44847JOHNSTONANASTROZOLE2013210414.0NRNRWOLFFLETROZOLE201335559.060NRIWATAEXEMESTANE2013314913.8NR50IWATAANASTROZOLE2013314911.1NR50FINNLETROZOLE201428110.27248DICKLERLETROZOLE2015317015.65274FINNLETROZOLE2016322214.54350 CONCLUSION. A combination of improved medical care and patient selection factors probably explain most of this progressive improvement in PFS obtained with the same therapeutic strategy. While in general, entry criteria have not changed significantly over time, more recent clinical trials addressing first line treatment of HR+ ABC are probably including a different population of patients. Exclusion of HER2 positive tumors and of unknown hormone receptor status patients as well as the percentage of patients without previous adjuvant exposure to endocrine therapy, for example, should be taken into account as they select for a more endocrine sensitive group of patients. This observation has implications in the planning of future studies, the estimation of sample size based in expected efficacy as well as the interpretation and generalization of the results to clinical practice. Citation Format: Debiasi M, Reinert T, Bines J, Barrios C. Time-evolution of the efficacy of first line aromatase inhibitors (AI) in hormone receptor positive (HR+) advanced breast cancer (ABC): A moving target [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-08-10.