A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer

Robertson, John F. R.; Jiang, Zefei; Di Leo, Angelo; Ohno, Shinji; Pritchard, Kathleen I.; Ellis, Matthew; Bradbury, Ian; Campbell, Christine

Abstract

Background
Fulvestrant, a selective estrogen receptor degrader, is approved for first- and second-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer (ABC).

Methods
Meta-analysis of randomized controlled trials (RCTs) evaluating fulvestrant 500 mg in postmenopausal hormone receptor-positive ABC, to evaluate differences in clinical benefit rate (CBR; proportion of patients experiencing best overall response of complete response, partial response, or stable disease for ≥ 24 weeks) between fulvestrant 500 mg and comparator endocrine therapies. Odds ratios (OR) and 95% confidence intervals (CI) for CBR were calculated; fixed effects (FE) models were constructed (first- and second-line data, alone and combined).

Results
Six RCTs were included. Four studies evaluated fulvestrant 500 mg vs. fulvestrant 250 mg; two evaluated fulvestrant 500 mg vs. anastrozole 1 mg. In total, 1054 and 534 patients were included (first- and second-line treatment, respectively). Analysis of OR and 95% CI of CBR by therapy line favored fulvestrant 500 mg vs. comparator therapy. Assessing all results combined in the FE model indicated significant improvement in CBR with fulvestrant 500 mg vs. comparator treatments (OR 1.33; 95% CI 1.13–1.57; p = 0.001). Restricting the FE model to therapy line demonstrated significant improvement in CBR vs. comparator treatments (OR 1.33; 95% CI 1.02–1.73; p = 0.035) for first-line, and a trend to improvement vs. comparator treatments (OR 1.27; 95% CI 0.90–1.79; p = 0.174) for second-line.

Conclusions
In postmenopausal patients with hormone receptor-positive ABC, fulvestrant 500 mg first-line was associated with significantly greater CBR (more patients benefiting from treatment) vs. comparator endocrine therapy.

Citation

Robertson, J. F. R., Jiang, Z., Di Leo, A., Ohno, S., Pritchard, K. I., Ellis, M., Bradbury, I., & Campbell, C. (2019). A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer. Breast Cancer, 26(6), 703-711. https://doi.org/10.1007/s12282-019-00973-4

• Journal Article Type: Article
• Acceptance Date: Apr 22, 2019
• Online Publication Date: May 11, 2019
• Publication Date: May 11, 2019
• Deposit Date: May 28, 2019
• Publicly Available Date: May 28, 2019
• Journal: Breast Cancer
• Print ISSN: 1340-6868
• Electronic ISSN: 1880-4233
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 6
• Pages: 703-711
• DOI: https://doi.org/10.1007/s12282-019-00973-4
• Keywords: Advanced breast cancer, Clinical benefit rate, Fulvestrant, Hormone receptor-positive, Meta-analysis
• Public URL: https://nottingham-repository.worktribe.com/output/2098013
• Publisher URL: https://link.springer.com/article/10.1007%2Fs12282-019-00973-4
• Additional Information: Received: 31 October 2018; Accepted: 22 April 2019; First Online: 11 May 2019; : ; : This work was supported by AstraZeneca. JFRR has received consulting fees from, and performed contracted research on behalf of, AstraZeneca, Bayer, Novartis, and Oncimmune; has given expert testimony for AstraZeneca; and holds stock with Oncimmune. ADL has received consulting fees from AstraZeneca, Novartis, Pfizer, and Roche; and has performed contracted research on behalf of AstraZeneca and Pfizer. SO has received honoraria from AstraZeneca, Chugai, Eisai, Kyowa Hakko Kirin, Novartis, Pfizer, Sanofi, and Taiho; and has performed contracted research on behalf of AstraZeneca, Daiichi Sankyo, and Taiho. KIP has received consulting fees from Amgen, AstraZeneca, Eisai, GlaxoSmithKline, Novartis, Pfizer, and Roche; and has performed contracted research on behalf of AstraZeneca, Eisai, Novartis, and Roche. ME has received consulting fees from AbbVie, AstraZeneca, Lilly, Merck, Nanostring, Novartis, Pfizer, and Zeno. ZJ, IB, and CC have declared that they have no conflicts of interest.
• Contract Date: May 28, 2019