This analysis combines data from six phase III trials investigating the role of endocrine-based therapies in the first-line setting of MBC to identify which factors may guide the clinical choice among available drugs.
For PFS, Hazard Ratio (HR) and 95% CI were reported. Subgroup meta-analysis was conducted stratifying by age, ECOG, ethnicity, prior chemotherapy or endocrine therapy exposure, measurable disease at the time of metastasis occurrence, visceral or bone only disease, time from the initial diagnosis of breast cancer to the metastasis onset. Random-effect model was used and heterogeneity was quantified by I² statistics. Test of interaction was performed to compare treatment effect in subgroups. Data analysis was performed using R Statistical Software version 3.4.3.
In absence of indirect comparison between cycline dependend kinase (CDK) 4/6 inhibitors (Palbociclib, Ribociclib, Abemaciclib) combined to nonsteroidal aromatase inhibitors (AIs) and Fulvestrant endocrine-based therapies, all these therapeutic options resulted in significant PFS benefit compared to AIs endocrine-monotherapy (HR: 0.74; 95% CI 0.67-0.80). Test of interaction showed similar treatment effects among sub-groups with the exception of Ethnicity and ECOG. Specifically, a longer PFS from CDK 4/6 inhibitors plus AIs strategies was observed in Asian (Asian HR: 0.38; 95% CI 0.20-0.72 versus non-Asian population HR: 0.61; 95% CI 0.50-0.75, p < 0.001) and ECOG≥1 patients (ECOG≥1 HR: 0.53; 95% CI 0.51-0.56 versus ECOG=0 HR: 0.60; 95% CI 0.49-0.74, p < 0.02).
CDK 4/6 inhibitors or Fulvestrant endocrine-based therapies as first-line treatment for postmenopausal women with HR+/HER2- MBC showed significant PFS improvement in comparison with AIs endocrine-monotherapy. Further indirect comparison by a network meta-analysis is needed to explore which patients may derive the greatest benefit from the different therapeutics options.
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