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

Abstract

PurposeTo 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).MethodsA 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.ResultsSixty 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.ConclusionsPalbociclib + 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 materialThe online version of this article (doi:10.1007/s10549-017-4404-4) contains supplementary material, which is available to authorized users.

Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis

“…20 Our data are consistent with previously published net work meta-analyses, although, to our knowledge, this analysis comprises the largest number of randomised controlled trials ever reported in hormone-receptor-positive, HER2-negative metastatic breast cancer and is the first comprehensive network meta-analysis to provide an indirect comparison of all CDK4/6 inhibitors plus aromatase inhibitors or fulvestrant and chemotherapybased regimens. [21][22][23][24] Moreover, this network metaanalysis is the first to include the BOLERO-6 trial, which, despite its small sample size, represents the only contemporary study directly comparing a hormone therapy plus targeted therapy (everolimus plus exemestane) versus chemo therapy (capecitabine), a regimen that is currently used in clinical practice (appendix p 18). 32 Results from the ongoing phase 3 PEARL trial are likely to provide additional evidence on this topic.…”

“…Some records were also retrieved via cross-references from published trials, the main international oncology guide lines, and most updated reviews or meta-analyses of therapeutic strategies in hormone-receptor-positive, HER2-negative metastatic breast cancer. [11][12][13][14][21][22][23][24] Phase 2 or 3 randomised controlled trials published in the form of full papers, or as abstracts if full papers were not available, were included in the analysis. No language restrictions were adopted for our search.…”

Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases

“…Chemotherapy is often used in patients with visceral metastases who are not in visceral crisis, despite worse clinical outcomes [ 20 ]. A network meta-analysis comparing palbociclib treatment with chemotherapy agents for the treatment of HR+/HER2− ABC showed that palbociclib plus fulvestrant and palbociclib plus letrozole demonstrate a trend in incremental efficacy compared with chemotherapy agents for the first-line and previously treated patients [ 21 ]. However, a head-to-head comparison between ET combined with a CDK4/6 inhibitor versus chemotherapy is currently lacking and as such the results of the network meta-analysis reported by Wilson et al should be interpreted with caution [ 21 ].…”

The Difference in Prognostic Outcomes Between De Novo Stage IV and Recurrent Metastatic Patients with Hormone Receptor-positive, HER2-negative Breast Cancer

“…The increasing application of novel cancer treatments including chemotherapy, endocrine therapy, and molecular-targeted therapy has improved the survival of metastatic BC patients (18)(19)(20). These treament advances have resulted in decreasing recurrence rates for early-stage breast cancer (3)(4)(5).…”