Abstract P3-11-05: Everolimus-exemestane (EE) vs palbociclib-fulvestrant (PF) or abemaciclib-fulvestrant (AF) or everolimus-fulvestrant (EF) in the treatment of metastatic HR+, HER2- metastatic breast cancer and prior aromatase inhibitors treatment. An indirect comparison with network meta-analysis
Authors: Gianni L , Arcangeli V , Gianni C , Stocchi L , Menghini L , Samorani D , Ridolfi C , Emiliano T , Tassinari D 
Published: February 2018

Background. Treatment options for patients with hormone receptor positive metastatic breast cancer (MBC) and prior treatment with aromatase inhibitors (AIs) include EE or PF. To date no direct comparison has been presented between EE and Fulvestrant plus Cyclin-dependent Kinase 4/6 (CDK4/6) inhibitors in this setting. The objective of this study was to compare the efficacy of EE to PF or AF or EF in the treatment of metastatic HR+, HER2- breast cancer pre-treated with AIs.

Methods. An indirect comparison with a network meta-analysis comparing EE with PF or AF or EF in the treatment of metastatic HR+, HER2- breast cancer pre-treated with AIs was performed. The Progression-Free-Survival (PFS) was the primary end point of all our indirect comparisons. Efficacy data were expressed as Hazard Ratio (HR) and 95% Confidence Interval (95CI), assuming an α-error of 5% as index of statistical significance.

Results. All the data of the BOLERO-2 trial, the Bachelot et al network meta-analysis (Breast Cancer Treat Rep 2014), the Paloma-3, the Monarch-2, and the prECOG trials were analyzed and indirectly compared in a network meta-analysis. 6 orders of comparison were performed: AF vs PL, PF vs EE, AF vs EE, EF vs AF, EF vs PF and EF vs EE. The pooled HR and 95%CI are reported in table1.

Table 1: difference in PFS between comparatorsComparisonsHR (95% CI)AF vs PF1.202 (0.87-1.661) p = 0.265PF vs EE1.674 (0.995-2.818) p = 0.89AF vs EE2.012 (1.09-3.714) p = 0.025EF vs AF1.085 (0.681-1.728) p = 0.731EF vs PF1.304 (0.804-2.117) p = 0.283EF vs EE2.183 (1.072-4.444) p = 0.031Everolimus-exemestane (EE), palbociclib-fulvestrant (PF), abemaciclib-fulvestrant (AF), everolimus-fulvestrant (EF).

Conclusions. Till today EE and PF represent active and approved treatments for patients with metastatic HR+, HER2- breast cancer treated with AIs. The results of Monarch-2 study with AF vs Fulvestrant and prECOG study with FE vs Fulvestrant were recently presented and were included in this metaanalysis, while the results of Ribociclib and Fulvestrant vs Fulvestrant (Monaleesa-3 study) are not currently available.

These studies generally show that combination of hormone therapies with Everolimus or CDK4/6 inhibitors are better than hormone-therapy alone, however no direct comparisons between these treatment combinations exist in literature. The results of our indirect treatment comparisons suggests that EE is similar and, in some cases, it may be even better than other treatment options. The optimal treatment strategy and sequence for patient with MBC and prior treatment with AIs should be evaluated in clinical trials. Meanwhile these data could be considered together with safety and the economic profile to help physicians in daily clinical practice.

Citation Format: Gianni L, Arcangeli V, Gianni C, Stocchi L, Menghini L, Samorani D, Ridolfi C, Emiliano T, Tassinari D. Everolimus-exemestane (EE) vs palbociclib-fulvestrant (PF) or abemaciclib-fulvestrant (AF) or everolimus-fulvestrant (EF) in the treatment of metastatic HR+, HER2- metastatic breast cancer and prior aromatase inhibitors treatment. An indirect comparison with network meta-analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-11-05.