351P - Safety of everolimus for women over 65 years of age with advanced breast cancer: 18-mo follow-up of BOLERO-2

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Geriatric Oncology
Presenter Michael Gnant
Authors M. Gnant1, S. Noguchi2, Y. Ito3, M. Piccart4, J. Baselga5, A. Panneerselvam6, T. Taran7, T. Sahmoud8, G.N. Hortobagyi9, K. Pritchard10
  • 1Deparment Of Surgery, Medical University of Vienna, 1090 - Vienna/AT
  • 2Department Of Breast And Endocrine Surgery, Osaka University, Osaka/JP
  • 3Department Of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo/JP
  • 4Medicine, Institut Jules Bordet, Brussels/BE
  • 5Massachusetts General Hospital Cancer Center And Harvard Medical School, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston/US
  • 6Sr Biostatistician, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 7Sr Global Clinical Leader, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 8Gbl Clin Program Head, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 9The University Of Texas Md Anderson Cancer Center, The University of Texas MD Anderson Cancer Center, Houston/US
  • 10Medical Oncology, Sunnybrook Odette Cancer Center, CA-M4N 3M5 - Toronto/CA



Hormone-receptor–positive (HR+) breast cancer (BC) refractory/resistant to nonsteroidal aromatase inhibitor (NSAI) may be treated with the steroidal AI exemestane (EXE), although there is no approved treatment standard. The BOLERO-2 trial showed that adding everolimus (EVE) to EXE significantly improved clinical benefit beyond that of EXE alone (Hortobagyi et al, SABCS 2011, Abstract S3-7). As many women with advanced BC are elderly (≥ 65 years), the efficacy and tolerability of EVE + EXE in this population are of interest.


BOLERO-2 is a phase 3, randomized trial comparing EVE (10 mg once daily) vs placebo (PBO), both plus EXE (25 mg once daily) in postmenopausal women with advanced HR+ BC progressing or recurring after NSAIs.


Baseline disease and prior treatment characteristics were balanced between study arms (N = 724). At 18 months' median follow-up, adding EVE to EXE significantly improved progression-free survival in patients < 65 (n = 449; 8.3 vs 2.9 mo; HR = 0.38; 95% CI = 0.30, 0.47) and ≥ 65 years (n = 275; 6.8 vs 4.0 mo; HR = 0.59; 95% CI = 0.43, 0.80). Overall incidence of adverse events (AEs) was marginally higher in patients ≥ 65 years (n = 272, safety population) compared with those < 65 years. Grade 3/4 AEs occurred in 50% of patients ≥ 65 years compared with 42% of patients < 65 years. Incidences of grade 3/4 stomatitis, rash, pneumonitis, and hyperglycemia in EVE-treated patients ≥ 65 years and those < 65 years were similar. Additional analysis using an age cutoff of 70 years also showed no meaningful differences in the efficacy/safety profile of EVE. Grade 3/4 AEs in patients ≥ 65 years reported among patients receiving EVE (n = 192) but not in those receiving PBO included anemia (9%), hyperglycemia (7%), stomatitis (9%), dyspnea (8%), pneumonitis (5%), neutropenia (3%), and hypertension (2%). These AEs were also reported at similar frequency in EVE-treated patients < 65 years.


Adding EVE to EXE was effective and well tolerated overall and, in elderly patients with advanced BC, grade 3/4 AEs were uncommon and manageable. Overall, AEs were consistent with the known safety profile of EVE.


M. Gnant: Research support from GSK, Sanofi-Aventis, Novartis, and Roche, consultant to Merrion and Novartis, and received honoraria & travel support from Amgen, Pfizer, Novartis, GSK, Bayer, Sandoz, AstraZeneca, and GenomicHealth.

S. Noguchi: S. Noguchi received grant support from AstraZeneca, BMS, Chugai, GSK, Novartis, Pfizer, Sanofi-Aventis, and Takeda, and honoraria (speaking, advisory boards, etc.) from AstraZeneca, Chugai, GSK, Novartis, Pfizer, Sanofi-Aventis, and Takeda.

M. Piccart: Board for PharmaMar, consultant Sanofi-Aventis, Amgen, BMS, GSK, Boehringer, Roche, & Bayer, grant support Pfizer, Amgen, Bayer, Boehringer, BMS, GSK, Roche, & Sanofi-Aventis, honoraria Bayer, BMS, GSK, Boehringer, Roche, Amgen, & AstraZeneca.

J. Baselga: J. Baselga is a consultant to Novartis, Roche, Merck, Sanofi-Aventis, Verastem, Bayer, Chugai, Exelixis, Onyx, and Constellation.

A. Panneerselvam: Employee of Novartis with stock/stock options.

T. Taran: Employee of Novartis with stock/stock options.

T. Sahmoud: Employee of Novartis with stock/stock options.

G.N. Hortobagyi: Member of the Scientific Advisory Board of Allergan, is a consultant to Allergan, Novartis, Genentech, and Sanofi-Aventis, has received grant support from Novartis, and has received travel expense reimbursement from Novartis, Genentech, and Sanofi-Aventis.

K. Pritchard: Consult sanaven AZE Roche PFE NVR ABR AMG GSK res funding NCICCT Grp contracted AZE BMS SanAven AMG PFE NVR GSK & OrthoBio honoraria & Spkr B SanAven AZE PFE Roche NVR & AMG paid expert test SanAven AZE & GSK AdCom SanAven AZE Roche PFE NVR GSK & AMG.

All other authors have declared no conflicts of interest.