OBJECTIVES: Palbociclib is a novel CDK4/6 inhibitor approved in the United States for HR+/ HER2- advanced/metastatic breast cancer (ABC/MBC) in combination with letrozole as initial endocrine-based therapy (first-line) in postmenopausal women, or with fulvestrant (second-line) in women with disease progression following endocrine therapy. However, limited data are available on the efficacy of palbociclib combinations compared to other endocrine therapies. We compared progressionfree survival (PFS) hazard ratio (HR) of palbociclib combinations against first- and second-line endocrine therapies using a mixed-treatment comparison (MTC) metaanalysis of randomized, controlled trials (RCTs).
METHODS: A systematic literature review conducted by two independent reviewers identified relevant RCTs in ABC/ MBC. Separate networks were developed for palbociclib plus letrozole and palbociclib plus fulvestrant. MTC analyses were conducted using a Bayesian approach. Based on output from MTC, treatment rankings were established using the surface under the cumulative ranking curve (SUCRA).
RESULTS: Sixty-four unique studies met inclusion criteria. Because of sparse networks, fixed-effects model results are reported. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all first-line comparators, with the following posterior median PFS HRs and 95% credible intervals (CrI): anastrozole 1 mg, 0.58 (0.42-0.83); and tamoxifen 20 or 40 mg, 0.41 (0.31-0.53). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and was associated with significantly longer PFS than the second-line comparators: anastrozole 1 mg, 0.37 (0.27-0.50); letrozole 2.5 mg, 0.36 (0.22-0.60); fulvestrant 250 mg, 0.36 (0.27-0.48); fulvestrant 500/250 mg, 0.41 (0.23-0.68); and exemestane 25 mg, 0.39 (0.23-0.64). There was no significant difference in the PFS HR for palbociclib plus fulvestrant compared to everolimus plus exemestane (1.03; 95%, 0.58-1.76).
CONCLUSIONS: The MTC results suggest that palbociclib plus letrozole and palbociclib plus fulvestrant are associated with significantly improved PFS compared with all first-line and most second-line endocrine treatments for ABC/MBC.
