Abstract P6-10-03: Comparative efficacy of everolimus in combination with exemestane and chemotherapy for advanced breast cancer in terms of progression-free survival

Abstract

Background: For hormone receptor-positive (HR+) advanced breast cancer (ABC), guidelines recommend endocrine therapy as the preferred option even in the presence of visceral disease. If there is evidence of endocrine resistance or rapidly progressive disease requiring a fast response then chemotherapy is recommended. The randomized controlled trial (RCT) BOLERO-2 demonstrated that everolimus plus exemestane (EVE+EXE) more than doubled median progression-free survival (PFS) compared with placebo+EXE while still maintaining quality of life in HR+/HER2- ABC patients who recurred or progressed during or after non-steroidal aromatase inhibitors (NSAIs). EVE+EXE offers a viable new line of therapy which can delay treatment with chemotherapy. Therefore, comparative evidence of EVE+EXE versus chemotherapies is relevant. In addition, such data will provide useful information for health technology assessment. Objective: 1) Assess the feasibility of network-meta-analysis (NMA) to compare the efficacy of EVE+EXE with chemotherapies in ABC in terms of PFS. 2) If feasible, to conduct the NMA. Methods: A systematic review of EMBASE, Medline, and Cochrane was performed to identify RCTs concerning the efficacy of everolimus, alternative hormonal therapies, and alternative chemotherapies for ABC in terms of PFS in order to facilitate an indirect comparison of everolimus versus chemotherapy. PFS data from published Kaplan-Meier curves for each treatment and RCT were synthesized and indirectly compared with random effects Bayesian Weibull network-meta-analysis (NMA) models. Analyses were performed assuming treatment effects as expressed with hazard ratios vary over time. Results: Based on a search of 6271 citations 24 RCTs were included. Differences across RCTs were identified in terms of age, post-menopausal status, receptor status, prior exposure to hormonal and chemotherapy, and types of hormonal therapies, visceral metastases, and performance status. Despite the limitations due to these differences, a NMA was performed to provide a broad estimate regarding comparative PFS for everolimus versus chemotherapy to inform current practice. Results of NMA in terms of mean PFS (i.e. area under the curve) up to 20 months are presented in Table 1. Sensitivity analyses will be performed to explore the impact of these differences on the robustness of the results. Table 1. Mean PFS until 20 months as obtained with NMATreatmentMean PFS time up to 20 months95% Credible Interval95% Credible IntervalEpirubicin6.162.5312.17Liposomal doxorubicin6.663.1212.00Paclitaxel7.103.7811.90Pegylated liposomal doxorubicin7.143.0913.56Doxorubicin7.353.9612.09Vinorelbine7.552.9914.28Docetaxel7.924.3712.45Capecitabine9.905.0316.67Nab paclitaxel10.105.4215.75Exemestane+ Everolimus12.216.2116.98 Conclusions: It is feasible to conduct NMA, however, differences in patient characteristics identified among studies are likely to have resulted in over or underestimation of the relative treatment effects. Based on the NMA, EVE+EXE is expected to be at least as efficacious as selected chemotherapies regarding PFS. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-10-03.

Everolimus-Based Therapy versus Chemotherapy among Patients with HR+/HER2− Metastatic Breast Cancer: Comparative Effectiveness from a Chart Review Study

“…The present comparative effectiveness findings are consistent with recent studies showing that HR+/HER2− mBC patients treated with everolimus-based therapy tended to have better OS [ 17 , 18 ] and PFS [ 19 ] than those treated with chemotherapy. For example, using a small sample of HR+/HER2− mBC patients, Pouget et al showed that everolimus plus endocrine therapy resulted in significantly longer OS than chemotherapy for patients pretreated with two or fewer lines of therapies for mBC [ 17 , 18 ].…”

“…For example, using a small sample of HR+/HER2− mBC patients, Pouget et al showed that everolimus plus endocrine therapy resulted in significantly longer OS than chemotherapy for patients pretreated with two or fewer lines of therapies for mBC [ 17 , 18 ]. Cope et al (2013) conducted a network meta-analysis of available mBC clinical trials and concluded that despite differences in patient characteristics across studies, everolimus/exemestane combinational therapy was associated with the longer mean PFS until 20 months compared to commonly-used chemotherapies such as capecitabine, doxorubicin, paclitaxel, and vinorelbine [ 19 ]. Future head-to-head clinical trial evidence will help further assess the comparative efficacy of everolimus-based therapy compared to chemotherapy.…”

“…A network meta-analysis of previous mBC trials also found that everolimus/exemestane combinational therapy was associated with comparable or better PFS compared to some commonly-used chemotherapy; however, findings in clinical trial settings may not represent the real-world comparative effectiveness. In addition, this analysis also had inherent limitations due to indirect comparisons of treatments from different studies with heterogeneous designs and patient populations [ 19 ].…”