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

Robertson, John F.R.; Paridaens, Robert J.; Lichfield, Jasmine; Bradbury, Ian; Campbell, Christine

Abstract

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%–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[less than] 0·001). The duration of clinical benefit was not significantly increased by AIs (hazard ratio [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.

Citation

Robertson, J. F., Paridaens, R. J., Lichfield, J., Bradbury, I., & Campbell, C. (2021). 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. European Journal of Cancer, 145, 19-28. https://doi.org/10.1016/j.ejca.2020.11.038

• Journal Article Type: Article
• Acceptance Date: Dec 1, 2020
• Online Publication Date: Jan 5, 2021
• Publication Date: Mar 1, 2021
• Deposit Date: Dec 7, 2020
• Publicly Available Date: Jan 6, 2022
• Journal: European Journal of Cancer
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 145
• Pages: 19-28
• DOI: https://doi.org/10.1016/j.ejca.2020.11.038
• Public URL: https://nottingham-repository.worktribe.com/output/5125338
• Publisher URL: https://www.ejcancer.com/article/S0959-8049(20)31375-7/abstract