Systematic review and network meta-analysis comparing palbociclib with chemotherapy agents for the treatment of postmenopausal women with HR-positive and HER2-negative advanced/metastatic breast cancer

PURPOSE: To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment for advanced disease (first line) or whose disease progressed after prior endocrine therapy or chemotherapy (second line). METHODS: A systematic search identified randomized controlled trials (RCTs) published from January 2000 to January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or chemotherapy agents + biological therapies in the first- and second-line treatment of postmenopausal women with HR+/HER2− ABC/MBC. The main outcome of interest was progression-free survival (PFS)/time to progression (TTP). Bayesian network meta-analyses (NMAs) and pairwise meta-analyses were conducted. Heterogeneity and inconsistency were assessed. RESULTS: Sixty RCTs met eligibility criteria and were stratified by line of therapy. In the first line, palbociclib + letrozole showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (95% CrI 0.11–0.72)] and mitoxantrone [HR 0.28 (0.13–0.61)], and trended toward improvements versus paclitaxel [HR 0.59 (0.19–1.96)], docetaxel [HR 0.51 (0.14–2.03)] and other monotherapy or combination agents (HRs ranging from 0.24 to 0.99). In the second line, palbociclib + fulvestrant showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (0.13–0.65)], mitoxantrone [HR 0.26 (0.12–0.53)], and pegylated liposomal doxorubicin [HR 0.19 (0.07–0.50)], and trended toward improvements versus paclitaxel [HR 0.48 (0.16–1.44)], docetaxel [HR 0.71 (0.24–2.13)] and other monotherapy or combination agents (HRs ranging from 0.23–0.89). NMA findings aligned with direct evidence and were robust to sensitivity analyses. CONCLUSIONS: Palbociclib + letrozole and palbociclib + fulvestrant demonstrate trends in incremental efficacy compared with chemotherapy agents for the first- and second-line treatment of HR +/HER2− ABC/MBC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-017-4404-4) contains supplementary material, which is available to authorized users.