title: First-line bevacizumab in combination with weekly paclitaxel for metastatic breast cancer: efficacy and safety results from a large, open-label, single-arm Japanese study.
abstract: Despite extensive evaluation of first-line bevacizumab-containing therapy in randomized trials in locally recurrent/metastatic breast cancer (LR/mBC), data from Japanese populations are limited. We conducted a phase II study exclusively in Japanese patients to evaluate bevacizumab combined with weekly paclitaxel. Patients with HER2-negative measurable LR/mBC who had received no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg, days 1 and 15, in combination with paclitaxel 90 mg/m(2), days 1, 8, and 15, repeated every 4 weeks, until disease progression, unacceptable toxicity, or patient/physician decision. Co-primary endpoints of this single-arm open-label phase II study were progression-free survival (PFS) and safety. A total of 120 patients (median age 55 years) received study therapy. At the time of data cut-off, the median duration of therapy was 11.1 months (range 0.5-24.7 months). Median PFS was 12.9 months (95% CI: 11.1-18.2) according to Independent Review Committee assessment and 14.9 months by investigator assessment. Median PFS was 9.6 months in the subgroup of 38 patients with triple-negative LR/mBC. The overall response rate was 74% (95% CI: 64.5-81.2%). Median overall survival (OS) was 35.8 months (95% CI: 26.4-not estimated) and the 1-year OS rate was 88.9% (95% CI: 83.2-94.6). The regimen was well tolerated and the safety profile was generally consistent with previous reports of bevacizumab-paclitaxel combination therapy. Grade 3 hypertension was reported in 17% of patients. Grade 4 hypertension, grade 3/4 proteinuria, and gastrointestinal perforation were absent. There were no new bevacizumab safety signals. In 50 patients (42%), treatment was continued for ≥ 1 year.
  
  
  CONCLUSIONS
  The high activity of first-line bevacizumab in combination with weekly paclitaxel observed in our study confirms the results of the E2100 trial. Our results suggest that the activity and tolerability of first-line bevacizumab-containing regimens demonstrated in E2100 can be reproduced in Japanese populations.
authors.affiliation: Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime 791-0280, Japan. kaogi@shikoku-cc.go.jp
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohno
authors.forename: Takashi
authors.initials: T
authors.lastname: Oda
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kashiwaba
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Shunji
authors.initials: S
authors.lastname: Kamigaki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ueno
authors.forename: Shigemitsu
authors.initials: S
authors.lastname: Takashima
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007564:Japan; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human