Progression-free survival with endocrine-based therapies following progression on non-steroidal aromatase inhibitor among postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative metastatic breast cancer: a network meta-analysis

Abstract

Objective: To quantify the comparative efficacy of currently available endocrine-based therapies (ETs) for postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2−) metastatic breast cancer (mBC) after non-steroidal aromatase inhibitor (NSAI) progression.

Design: Network meta-analysis (NMA).

Methods: Randomized clinical trials of ETs for HR+/HER2− mBC were identified via a systematic literature review using MEDLINE, Embase, Cochrane Library and key conference proceedings. All trials met the following inclusion criteria: (1) included women with HR+/HER2− mBC; (2) previous treatment with ETs or chemotherapy as first-line therapy; (3) treatment with ET as monotherapy or in combination with targeted therapy; (4) progression-free survival (PFS) was reported; and (5) published in 2007 (when HER2 testing became standardized) or later. Regimens were compared using pairwise hazard ratios (HRs) and 95% credible intervals (CrIs) of PFS obtained from a Bayesian NMA. Treatments with different approved dosages were pooled into the same arm; anastrozole and exemestane were pooled as aromatase inhibitors (AIs) due to clinical similarities.

Results: A total of 4 trials and 6 regimens (palbociclib + fulvestrant, everolimus + fulvestrant, everolimus + AI, fulvestrant + AI, fulvestrant and AI) were eligible for inclusion. Palbociclib + fulvestrant and everolimus + AI had 50% and 55% reduced hazard of progression or death vs. AI (95% CrI upper bound ≤1), respectively. Palbociclib + fulvestrant, everolimus + AI and everolimus + fulvestrant had 54%, 58% and 40% reduced hazard vs. fulvestrant (95% CrI upper bound ≤1), while palbociclib + fulvestrant and everolimus + AI had 52% and 55% reduced hazard vs. fulvestrant + AI (95% CrI upper bound ≤1), respectively.

Conclusion: Postmenopausal women with HR+/HER2− mBC who had previously failed an NSAI and received palbociclib + fulvestrant, everolimus + AI or everolimus + fulvestrant had longer PFS compared to those who received fulvestrant or AI alone.

Keywords:

• Metastatic breast cancer
• HR+/HER2−
• endocrine-based therapies
• network meta-analysis

Transparency

Declaration of funding

Author contributions: All authors contributed to study design, data analysis and interpretation as well as manuscript development, drafting and review. All authors have read and approved the manuscript being submitted. All authors agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

R.A., O.P.L., Z.Z. and J.X. have disclosed that they are employees of Analysis Group, which has received consultancy fees from Novartis Pharmaceuticals Corporation for this study. D.T., D.C. and A.A.D. have disclosed that they are employees of Novartis Pharmaceuticals Corporation and own stock or stock options. P.A.N. has disclosed that she received consulting fees from Novartis Pharmaceuticals Corporation.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgements

We would like to thank Cinzia Metallo PhD, an employee of Analysis Group, for medical writing assistance.