Comparative efficacy of everolimus versus fulvestrant for hormone-receptor–positive (HR+) advanced breast cancer (ABC) following progression/recurrence after first-line treatment: A network meta-analysis.

Breast Cancer - HER2/ER
Session Type and Session Title: 
This abstract will not be presented at the 2013 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr e11602)
Thomas Denis Bachelot, Guy Heinrich Maria Jerusalem, Maria Cikalo, Rachael McCool, Sarah King, Steven Duffy, Julie Glanville, Danielle Varley, Jie Zhang; Centre Léon Bérard, Lyon, France; Centre Hospitalier Universitaire Sart Tilman Liege and University of Liege, Liège, Belgium; York Health Economics Consortium, York, United Kingdom; Novartis Pharmaceuticals Corp, Florham Park, NJ

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Everolimus (EVE), an oral mammalian target of rapamycin (mTOR) inhibitor, is approved in combination with exemestane (EXE) to treat postmenopausal women (PMW) with HR+, human epidermal growth factor receptor-2–negative (HER2) ABC that progressed after nonsteroidal aromatase inhibitor therapy. Fulvestrant (FUL), an estrogen receptor antagonist, is another treatment option for PMW previously treated with endocrine therapy. However, the comparative efficacy of EVE + EXE vs FUL is unknown. Methods: Six randomized, controlled trials in HR+, HER2ABC patients were identified by systematic literature review (Cochrane library, National Horizon Scanning Centre, and NICE Web sites) that formed a network permitting indirect comparisons of EVE + EXE or EVE + tamoxifen (TAM) vs FUL: BOLERO-2, CONFIRM, EFECT, Paridaens (2008), SoFEA, and TAMRAD. All 6 trials had EXE, TAM, or FUL 250 mg as the common comparator to form the network. Relative efficacy of EVE and FUL was obtained using a Bayesian network meta-analysis based on these 6 trials. The primary endpoint was local assessment of progression-free survival (PFS) or time to progression (TTP). The hazard ratio (HR) of EVE + EXE relative to FUL and its 95% credible intervals (CrI) were calculated. Evidence of a difference between treatments is suggested by the 95% CrI not including 1. A HR <1 indicates that the hazard rate is higher in the comparator group and that the treatment is more effective. Results: EVE + EXE was found to be more efficacious for PFS/TTP than FUL 250 mg (HR = 0.47; 95% Crl, 0.38-0.58) and more efficacious than FUL 500 mg (HR = 0.59; 95% Crl, 0.45-0.77). EVE + TAM was found to be numerically better for PFS/TTP than FUL 250 mg (HR = 0.65; 95% Crl, 0.40-1.04) and numerically better than FUL 500 mg (HR = 0.81; 95% Crl, 0.49-1.33). Conclusions: The indirect evidence from this analysis suggests that EVE in combination with EXE is more efficacious than FUL 250 and 500 mg in PMW with HR+, HER2 ABC that progresses after endocrine therapy. These data should be interpreted with caution as there is no randomized trial that directly compares EVE + EXE vs FUL.