title: Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1.
abstract: The current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial.
  
  
  
  Postmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel. The two primary end points were investigator-assessed progression-free survival (PFS) in the full population and in the hormone receptor-negative (HR-) subpopulation. Secondary end points included assessment of the objective response rate, the clinical benefit rate, and safety.
  
  
  
  In the Asian subset, median PFS was similar in the everolimus (n = 198) and placebo (n = 105) arms in the full analysis set (hazard ratio = 0.82 (95% CI 0.61-1.11)). In the HR- subpopulation, everolimus prolonged median PFS by 10.97 months vs placebo (25.46 vs 14.49 months; hazard ratio = 0.48 (95% CI 0.29-0.79)). In the everolimus arm of the Asian subset, the most common adverse events of any grade were stomatitis (62.2%), diarrhea (48.0%), rash (43.4%) and neutropenia (42.3%). Neutropenia (grade 3: 27.6%; grade 4: 4.6%) and decreased neutrophil count (grade 3: 11.2%; grade 4: 3.6%) were the most frequent grade 3/4 adverse events. Serious adverse events included pneumonia (5.1%), pneumonitis (3.1%), and interstitial lung disease (3.1%). There were three deaths (1.5%) during treatment in the everolimus arm vs none in the placebo arm.
  
  
  
  The efficacy and safety of everolimus plus trastuzumab and paclitaxel as first-line treatment for HER2+ advanced breast cancer in the Asian subset was consistent with that reported previously in the overall population.
  
  
  
  ClinicalTrials.gov, NCT00876395 . Registered on 2 April 2009.
authors.affiliation: Department of Breast Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. toi@kuhp.kyoto-u.ac.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.affiliation: Department of Breast Surgery, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shao
authors.affiliation: University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Hurvitz
authors.affiliation: Taipei Veterans General Hospital, National Yang Ming University, Taipei, Taiwan.
authors.forename: Ling-Ming
authors.initials: LM
authors.lastname: Tseng
authors.affiliation: Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Kunwei
authors.initials: K
authors.lastname: Shen
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Donggeng
authors.initials: D
authors.lastname: Liu
authors.affiliation: Jiangsu Cancer Hospital, 210009, Nanjing, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Medical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China.
authors.forename: Binghe
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University Hangzhou, Hangzhou, Zhejiang Province, China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Breast Cancer, National Cancer Center, Gyeunggi-do, South Korea.
authors.forename: Keun Seok
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Clinical Oncology, Tuen Mun Hospital, Tuen Mun, Hong Kong.
authors.forename: Ting Ying
authors.initials: TY
authors.lastname: Ng
authors.affiliation: Novartis Pharma SAS, Rueil-Malmaison, France.
authors.forename: Antonia
authors.initials: A
authors.lastname: Ridolfi
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Noel-Baron
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Francois
authors.initials: F
authors.lastname: Ringeisen
authors.affiliation: Beijing 307 Hospital of PLA, Beijing, China.
authors.forename: Zefei
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000068338:Everolimus / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D019233:Retreatment; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000068338:Everolimus; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: Advanced breast cancer; Asian; BOLERO-1; Everolimus; HER2; Metastatic breast cancer