324PD - Efficacy and safety of everolimus in postmenopausal women with advanced breast cancer (BOLERO-2): effect of visceral metastases and prior endocrine...

Date 01 October 2012
Event ESMO Congress 2012
Session Breast cancer, locally advanced and metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Mario Campone
Authors M. Campone1, S. Noguchi2, K. Pritchard3, H.S. Rugo4, G.N. Hortobagyi5, J. Baselga6, A. Panneerselvam7, T. Taran8, T. Sahmoud9, M. Piccart10
  • 1Medical Oncology, Institut de Cancérologie de l’Ouest - René Gauducheau, Herblain/FR
  • 22department Of Breast And Endocrine Surgery, Osaka University, Osaka/JP
  • 3Medical Oncology, Sunnybrook Odette Cancer Center, CA-M4N 3M5 - Toronto/CA
  • 44University of California San Francisco, San Francisco/US
  • 55the University Of Texas Md Anderson Cancer Center, The University of Texas MD Anderson Cancer Center, Houston/US
  • 6Massachusetts General Hospital Cancer Center And Harvard Medical School, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston/US
  • 7Biostatistician, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 8Bu Oncology, Novartis Pharmaceuticals, Florham Park/US
  • 9Gbl Clin Program Head, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 10Medicine, Institut Jules Bordet, Brussels/BE



Postmenopausal women with hormone receptor-positive (HR+) breast cancer (BC) who relapse or progress on a nonsteroidal aromatase inhibitor (NSAI) have limited treatment options. At a median follow-up of 18 months, BOLERO-2 demonstrated that everolimus (EVE), an oral mammalian target of rapamycin (mTOR) inhibitor, plus exemestane (EXE), a steroidal aromatase inhibitor, prolonged progression-free survival (PFS) compared with EXE alone in this setting (7.8 vs 3.2 mo, respectively; hazard ratio [HR] = 0.45 [95% confidence interval (CI) = 0.38, 0.54]; log-rank P < .0001).


BOLERO-2 is a phase 3, double-blind, randomized study that compared EVE (10 mg/d) + EXE (25 mg/d; n = 485) versus placebo (PBO) + EXE (n = 239) in postmenopausal women with advanced HR+ HER2 BC who had progression or recurrence after NSAI therapy. The primary endpoint was PFS by local investigator assessment. In view of the limited efficacy of endocrine therapies in patients with visceral involvement, EVE + EXE was evaluated in patient subgroups defined by the presence of visceral metastases (including lung, liver, spleen, pleural effusions, pericardial effusion, peritoneum, ascites, ovary and central nervous system).


At a median follow-up of 18 months, adding EVE to EXE prolonged median PFS versus PBO + EXE in patients with visceral metastases (n = 406; 6.8 vs 2.8 mo, respectively; HR = 0.47 [95% CI = 0.37, 0.60]). Similarly, EVE + EXE extended PFS in patients without visceral metastases (n = 318; 9.9 vs 4.2 mo for PBO + EXE; HR = 0.41 [95% CI = 0.31, 0.55]). Patients with visceral involvement had shorter PFS compared with patients with bone-only disease regardless of treatment. Nonetheless, PFS improvements with EVE + EXE were similar in patients with visceral and bone-only disease (n = 151; 12.9 vs 5.3 mo for PBO + EXE; HR = 0.33 [95% CI = 0.21, 0.53]).


Adding EVE to EXE markedly extended PFS by ≥ 4 mo among patients with advanced HR+ HER2 BC regardless of the presence of visceral metastases.


M. Campone: M. Campone is a consultant to and has received honoraria from Novartis.

S. Noguchi: S Noguchi has received grant support and honoraria from AstraZeneca, Chugai, Pfizer, sanofi-aventis, GSK, Taiho, Novartis, and Takeda.

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.

H. Rugo: H. Rugo has received grant support from Novartis, Pfizer, and Merck, and has received travel support from Novartis.

G.N. Hortobagyi: Member of the Scientific Advisory Board of Allergan, consultant to Allergan, Novartis, Genentech, and sanofi-aventis, received grant support from Novartis, and travel expense reimbursement from Novartis, Genentech, and sanofi-aventis.

J. Baselga: J Baselga is a consultant to Novartis, Roche, Merck, sanofi-aventis, Verastem, Bayer, Chugai, Exelixis, Onyx, Constellation.

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

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

T. Sahmoud: An employee of Novartis with stock/stock options.

M. Piccart: Board PharmaMar, consultant sanofi-aventis, Amgen, BMS, GSK, Boehringer, Roche, & Bayer, & grant Pfizer, Amgen, Bayer, Boehringer, BMS, GSK, Roche, & sanofi-aventis, honoraria Bayer, BMS, GSK, Boehringer, Roche, Amgen, sanofi-aventis, & AZE.