Abstract P4-13-01: Endocrine treatment for hormone receptor-positive advanced breast cancer patients with endocrine-sensitive or endocrine-resistant disease: A systematic review and network meta-analysis
Authors: Brandão M , Maurer C , Ziegelmann P , Pondé N , Ferreira AR , Martel S , Piccart-Gebhart M , Debiasi M , de Azambuja E , Lambertini M 
Published: May 2019

Abstract
Background: For patients with hormone receptor-positive (HR+) advanced breast cancer (ABC), the choice of endocrine treatment should be based on the best available evidence. However, no direct head-to-head comparison of all tested regimens is currently available. This network meta-analysis aims at providing detailed inference-based data to guide decision making on endocrine therapy for HR+ ABC patients in two different clinical scenarios: endocrine-sensitive and endocrine-resistant ABC, as defined by the ABC guidelines criteria.
Methods: Phase II/III randomized clinical trials published or presented up to June 15, 2018 and comparing two or more different endocrine treatments (with or without associated targeted therapies) for HR+, HER2-negative ABC patients were included, irrespective of treatment line. Relative treatment effects were pooled as hazard ratios (HRs) and modeled in a network meta-analysis using a Bayesian framework with fixed-effects models in order to infer the best approach. The main outcomes were progression-free survival (PFS) and overall survival (OS). Four separate analyses were carried out: PFS and OS networks in both endocrine-sensitive and endocrine-resistant populations.
Results: A total of 26 trials were included in this meta-analysis (N=11330 patients). In the endocrine-sensitive setting, 12 trials were included in the PFS network (N=5200 patients; 10 different regimens) and 3 trials in the OS network (N=1295; 3 regimens). In terms of PFS, the combination of Fulvestrant 500 mg (F500)+CDK4/6 inhibitors (CDKi) had a 80% probability of being the most effective treatment, followed by aromatase inhibitor (AI)+CDKi (17% chance of being the best approach). The HR for the comparison between F500+CDKi vs. AI+CDKi was 0.82 (95% credibility interval [CrI] 0.54-1.25). Regarding OS, the AI+CDKi approach had a 63% chance of being the most effective regimen, followed by F500 (36% likelihood) – the comparison between the two regimens yielded a HR of 0.93 (95% CrI 0.61-1.40). In the endocrine-resistant setting, 18 trials were included in the PFS network (N=6130; 20 regimens) and 7 in the OS network (N=2701; 10 regimens). For PFS, F500+CDKi had a 59% probability of being the most effective treatment, followed by F500+Everolimus (11% likelihood). The HR of the comparison between F500+CDKi vs. F500+Everolimus was 0.84 (95% CrI 0.57-1.25). In terms of OS, F500+FGFR inhibitors had a 29% chance of being the best treatment option, followed by AI+everolimus (24% likelihood) – the HR for the comparison of F500+FGFR inhibitors vs. AI+everolimus was 1.07 (95% CrI 0.36-3.18).
Conclusion: This network meta-analysis provides for the first time a comparison of all tested treatment options for HR+ ABC patients in both endocrine-sensitive and endocrine-resistant settings. In terms of PFS, F500+CDKi appears to be the best treatment option for both disease settings. As for OS, AI+CDKi is possibly the best choice for endocrine-sensitive ABC patients. Concerning endocrine-resistant disease, F500+FGFR inhibitors may be an effective regimen which should be further studied, while AI+everolimus remains the best available option in this setting.
Citation Format: Brandão M, Maurer C, Ziegelmann P, Pondé N, Ferreira AR, Martel S, Piccart-Gebhart M, Debiasi M, de Azambuja E, Lambertini M. Endocrine treatment for hormone receptor-positive advanced breast cancer patients with endocrine-sensitive or endocrine-resistant disease: A systematic review and network meta-analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-13-01.