Progression-free Survival With First-line Endocrine-based Therapies Among Postmenopausal Women With HR+/HER2- Metastatic Breast Cancer: A Network Meta-analysis

OBJECTIVE:

To quantify the comparative efficacy of currently available endocrine-based therapies (ETs) for postmenopausal women with HR+/HER2- mBC after 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) 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 have 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.