[S3-7] Everolimus for Postmenopausal Women with Advanced Breast Cancer: Updated Results of the BOLERO-2 Phase III Trial.

Hortobagyi GN, Piccart M, Rugo H, Burris H, Campone M, Noguchi S, Gnant M, Pritchard KI, Vittori L, Mukhopadhyay P, Sahmoud T, Lebwohl D, Baselga J. The University of Texas, MD Anderson Cancer Center, Houston, TX; Jules Bordet Institute (Institut Jules Bordet), Brussels, Belgium; University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA; Sarah Cannon Research Institute, Nashville, TN; Institut de Cancérologie de l'Ouest - René Gauducheau, Centre de Recherche en Cancérologie, Nantes Saint Herblain, France; Osaka University, Osaka, Japan; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto, Canada; Novartis Pharma AG, Basel, Switzerland; Novartis Pharmaceuticals Corporation, East Hanover, NJ; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA

Background: The mTOR pathway is constitutively activated in hormone-resistant advanced breast cancer (ABC). In phase II trials, everolimus (EVE) showed promising efficacy both as monotherapy and in combination with endocrine therapy in patients with estrogen receptor–positive (ER+) ABC. This double-blind, placebo-controlled, phase III study evaluated EVE plus exemestane (EXE) in patients with ER+ ABC refractory to letrozole or anastrozole.
Patients and Methods: Eligible patients were randomized (2:1) to EXE (25 mg/day) with EVE (10 mg/day) or with matching placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, quality of life (QoL), and safety.
Results: 724 patients were randomized (485: EVE+EXE; 239: EXE). Baseline characteristics were well balanced; median age was 62 years, 56% had visceral involvement, and 84% had documented benefit from previous endocrine therapy, which included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy for advanced disease (25%). This analysis is based on 457 events and median follow-up of 12.5 months. PFS by investigator assessment showed a hazard ratio (HR) of 0.44 (95% CI: 0.36-0.53) and a median duration of 7.4 (EVE+EXE) vs 3.2 months (EXE) (P<1 × 10-16) and 12-month estimate of 31% vs 10%. PFS by central assessment showed an HR of 0.36 (95% CI: 0.28-0.45) and a median duration of 11.0 (EVE+EXE) vs 4.1 months (EXE) (P<1 × 10-16) and 12-month estimate of 48% vs 18%. Response rates and clinical benefit rate were also higher for EVE+EXE (12.0% vs 1.3% and 50.5% vs 25.5%). A total of 138 patients died; 17.3% in the EVE+EXE arm and 22.6% in the EXE arm.
The most common grade 3/4 adverse events were stomatitis (8% vs 1%), anemia (7% vs 1%), hyperglycemia (5% vs < 1%), dyspnea (4% vs 1%), and fatigue (4% vs 1%) for the EVE+EXE and EXE groups, respectively. Grade 3 pneumonitis was observed in patients receiving EVE (3% vs 0%). No difference in time to deterioration of QoL was observed. EVE increased EXE steady-state Cmin and Cmax levels by 45% and 64%, respectively, with no difference in estradiol levels. Serum markers of bone resorption and bone formation increased in the EXE arm and generally decreased in the EVE+EXE arm.
Conclusion: The addition of EVE to EXE is associated with significant and sustained prolongation of PFS. Adverse events were higher in the combination arm but manageable by dose interruption and/or reduction and did not affect QoL. EVE in combination with an aromatase inhibitor is a promising therapeutic option for women with hormone receptor–positive advanced breast cancer.

Thursday, December 8, 2011 11:00 AM

General Session 3 (9:30 AM-11:15 AM)

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