Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2

Shinzaburo Noguchi, Norikazu Masuda, Hiroji Iwata, Hirofumi Mukai, Jun Horiguchi, Puttisak Puttawibul, Vichien Srimuninnimit, Yutaka Tokuda, Katsumasa Kuroi, Hirotaka Iwase, Hideo Inaji, Shozo Ohsumi, Woo Chul Noh, Takahiro Nakayama, Shinji Ohno, Yoshiaki Rai, Byeong Woo Park, Ashok Panneerselvam, Mona El-Hashimy, Tetiana TaranTarek Sahmoud, Yoshinori Ito

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


Results: Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41–0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33–0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients.

Conclusion: Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR+/HER2 advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.

Background: The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR+) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757–62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported.

Methods: Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety.

Original languageEnglish
Pages (from-to)703-714
Number of pages12
JournalBreast Cancer
Issue number6
Publication statusPublished - 2014 Nov

Bibliographical note

Funding Information:
The BOLERO-2 trial was supported by Novartis Pharmaceuticals: ClinicalTrials.gov identifier NCT00863655. Funding for medical editorial support was also provided by Novartis. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Kristin E. Larsen, PhD, ProEd Communications, Inc., for medical editorial assistance with this manuscript. The BOLERO-2 trial was conducted in the USA, Japan, Canada, Brazil, Austria, Belgium, Czech Republic, France, Germany, Hungary, Italy, the Netherlands, Norway, Poland, Spain, Sweden, Turkey, UK, Egypt, Australia, China (Hong Kong), New Zealand, South Korea, and Thailand. We thank the patients, study site personnel, and the study team for their participation in the trial.

Publisher Copyright:
© 2013, The Author(s).

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)


Dive into the research topics of 'Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2'. Together they form a unique fingerprint.

Cite this