TY - JOUR
T1 - Progression-free Survival With First-line Endocrine-based Therapies Among Postmenopausal Women With HR+/HER2– Metastatic Breast Cancer:: A Network Meta-analysis
AU - Ayyagari, Rajeev
AU - Tang, Derek
AU - Patterson-Lomba, Oscar
AU - Zhou, Zhou
AU - Xie, Jipan
AU - Chandiwana, David
AU - Dalal, Anand A.
AU - Niravath, Polly Ann
N1 - Funding Information:
Funding for this research was provided by Novartis Pharmaceuticals Corporation. Writing support was provided by Cinzia Metallo, PhD, an employee of Analysis Group, Inc. All authors contributed to study design, literature search, data collection, interpretation of the study results, and manuscript writing. Drs. Ayyagari and Patterson-Lomba contributed to data analyses and figure creation. Appendix A
Publisher Copyright:
© 2018 Elsevier HS Journals, Inc.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/4
Y1 - 2018/4
N2 - Purpose: The comparative efficacy of endocrine-based therapies (ETs) for hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (mBC) is not well characterized. This network meta-analysis (NMA) synthesized available evidence on progression-free survival (PFS) with first-line ETs for postmenopausal HR+/HER2– mBC. Methods: A systematic literature review identified randomized controlled trials of first-line ETs. Pairwise hazard ratios and 95% credible intervals (CrIs) were obtained via a Bayesian NMA model. Subgroup NMAs were conducted among late progressors (disease-free interval ≥12 months from completion of [neo] adjuvant therapy with letrozole or anastrozole at the time of randomization) and de novo patients, defined as patients whose initial BC diagnosis is mBC. Findings: Five trials and 5 regimens (ribociclib + an aromatase inhibitor [AI] [LEE + AI], palbociclib + AI [Pal + AI], fulvestrant 250 mg + AI [Ful250 + AI], fulvestrant 500 mg [Ful500], and AI) were selected. LEE + AI, Pal + AI, Ful250 + AI, and Ful500 had significantly longer PFS versus AI (95% CrI upper-bound ≤1). LEE + AI had a 30% and 29%, and Pal + AI had a 31% and 30%, reduced hazard of progression or death versus Ful250 + AI and Ful500 (95% CrI upper-bound ≤1), respectively. The probability of being the most efficacious was 46% for LEE + AI and 54% for Pal + AI. In subgroup analyses among late progressors, LEE + AI had a 4% reduced hazard of progression or death versus Pal + AI but was not statistically significant. In the de novo analysis, Pal + AI and LEE + AI had a 29% and 40% reduced hazard of progression or death versus Ful500, respectively, but were not statistically significant. In both subgroup analyses, all therapies had significantly longer PFS compared with AI. Implications: Pal + AI, LEE + AI, Ful250 + AI, or Ful500 as first-line treatment for HR+/HER2– mBC had longer PFS than AI alone. Given the lack of head-to-head clinical trials comparing the efficacy of recently approved first-line ETs for HR+/HER2– mBC, these results have important clinical implications for the treatment of HR+/HER2– mBC in the first-line setting.
AB - Purpose: The comparative efficacy of endocrine-based therapies (ETs) for hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (mBC) is not well characterized. This network meta-analysis (NMA) synthesized available evidence on progression-free survival (PFS) with first-line ETs for postmenopausal HR+/HER2– mBC. Methods: A systematic literature review identified randomized controlled trials of first-line ETs. Pairwise hazard ratios and 95% credible intervals (CrIs) were obtained via a Bayesian NMA model. Subgroup NMAs were conducted among late progressors (disease-free interval ≥12 months from completion of [neo] adjuvant therapy with letrozole or anastrozole at the time of randomization) and de novo patients, defined as patients whose initial BC diagnosis is mBC. Findings: Five trials and 5 regimens (ribociclib + an aromatase inhibitor [AI] [LEE + AI], palbociclib + AI [Pal + AI], fulvestrant 250 mg + AI [Ful250 + AI], fulvestrant 500 mg [Ful500], and AI) were selected. LEE + AI, Pal + AI, Ful250 + AI, and Ful500 had significantly longer PFS versus AI (95% CrI upper-bound ≤1). LEE + AI had a 30% and 29%, and Pal + AI had a 31% and 30%, reduced hazard of progression or death versus Ful250 + AI and Ful500 (95% CrI upper-bound ≤1), respectively. The probability of being the most efficacious was 46% for LEE + AI and 54% for Pal + AI. In subgroup analyses among late progressors, LEE + AI had a 4% reduced hazard of progression or death versus Pal + AI but was not statistically significant. In the de novo analysis, Pal + AI and LEE + AI had a 29% and 40% reduced hazard of progression or death versus Ful500, respectively, but were not statistically significant. In both subgroup analyses, all therapies had significantly longer PFS compared with AI. Implications: Pal + AI, LEE + AI, Ful250 + AI, or Ful500 as first-line treatment for HR+/HER2– mBC had longer PFS than AI alone. Given the lack of head-to-head clinical trials comparing the efficacy of recently approved first-line ETs for HR+/HER2– mBC, these results have important clinical implications for the treatment of HR+/HER2– mBC in the first-line setting.
KW - HR positive/HER2 negative
KW - endocrine therapy
KW - metastatic breast cancer
KW - network meta-analysis
KW - progression-free survival
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85045129069&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045129069&partnerID=8YFLogxK
U2 - 10.1016/j.clinthera.2018.03.004
DO - 10.1016/j.clinthera.2018.03.004
M3 - Review article
C2 - 29609880
AN - SCOPUS:85045129069
VL - 40
SP - 628-639.e3
JO - Clinical Therapeutics
JF - Clinical Therapeutics
SN - 0149-2918
IS - 4
ER -