Meta-Analyses Of Phase 3 Randomised Controlled Trials Of Third Generation Aromatase Inhibitors Versus Tamoxifen As First-Line Endocrine Therapy In Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer

Background: Four randomised controlled trials (RCTs) in postmenopausal women with advanced breast cancer (ABC) comparing aromatase inhibitors (AIs) versus the selective estrogen receptor modulator tamoxifen, each individually reported significantly longer progression-free survival (PFS) but none showed a significant difference in overall survival (OS). In these trials between 6.8% and 55% of tumours were hormone receptor (HR) status unknown or negative. This meta-analysis restricted the comparison to HR-positive (HR+) tumours.Methods: Anonymised individual patient data were obtained from three RCTs, EORTC (exemestane versus tamoxifen), Study 0027 and Study 0030 (both anastrozole versus tamoxifen). For the remaining RCT (Femara Study PO25; letrozole versus tamoxifen), odds ratio (OR) or hazard ratio (HzR), with confidence intervals were obtained from the clinical study report, for patients with HR+ tumours, in addition to published data. In total, data were obtained from 2296 patients; 1560 (68%) had HR+ ABC.Findings: The OR for clinical benefit rate was 1.56, in favour of AIs (p < 0.001). The duration of clinical benefit was not significantly increased by AIs (HzR 0.88; p = 0.08). For PFS the HzR (0.82) was in favour of AIs (p = 0.007). However, for OS the HzR (1.05) was not significantly different between AIs and tamoxifen (p = 0.42).Interpretation: Although third generation AIs put significantly more patients into 'clinical benefit', their tumours were not controlled for significantly longer. Overall, while this resulted in a significantly greater PFS in favour of the AIs, this did not translate into improvement in OS. (C) 2020 The Author(s). Published by Elsevier Ltd.