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

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.