title: Implications of BRCA1 and BRCA2 mutations for the efficacy of paclitaxel monotherapy in advanced ovarian cancer.
abstract: BACKGROUND
  Preclinical data suggest that BRCA1 and BRCA2 (BRCA1/2)-mutated ovarian cancers (BMOC) are exquisitely sensitive to platinum-salts, but resistant to microtubule-stabilizing anticancer agents. The clinical relevance of these preclinical data is unclear, since there are currently no published data on the efficacy of single-agent taxane chemotherapy in patients with BMOC. A retrospective study was undertaken to investigate the clinical effects of paclitaxel monotherapy in patients with BMOC.
  
  
  METHODS
  Clinical data on responses and progression-free-survival (PFS) following paclitaxel (3-weekly/weekly) monotherapy in BMOC patients were collected from four cancer centres. Antitumour response was defined as RECIST partial or complete response (PR/CR), and clinical benefit was defined as PR/CR and stable disease (SD) lasting at least 18 weeks. Comparisons of the rate and duration of response and clinical benefit between categorical variables (e.g. platinum-sensitive versus platinum-resistant patients) were undertaken.
  
  
  RESULTS
  We identified 26 BMOC patients who received paclitaxel monotherapy for relapsed disease, of which 15/26 (58%) were platinum-sensitive and 11/26 (42%) were platinum-resistant. The response rate to paclitaxel monotherapy was 46% (12/26). Clinical benefit rate was significantly higher in platinum-sensitive than platinum-resistant patients (80% versus 36%, p=0.04). BMOC patients with platinum-sensitive disease had significantly longer median PFS compared with platinum-resistant patients (42 versus 21 weeks, p=0.003).
  
  
  CONCLUSIONS
  These data provide the first clinical evidence that paclitaxel monotherapy is active in BMOC and may be more effective in platinum-sensitive BMOC.
authors.affiliation: Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, United Kingdom.
authors.forename: David S P
authors.initials: DS
authors.lastname: Tan
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Yap
authors.forename: Margaret
authors.initials: M
authors.lastname: Hutka
authors.forename: Patricia
authors.initials: P
authors.lastname: Roxburgh
authors.forename: Jooern
authors.initials: J
authors.lastname: Ang
authors.forename: Susana
authors.initials: S
authors.lastname: Banerjee
authors.forename: Ewa
authors.initials: E
authors.lastname: Grzybowska
authors.forename: Charlie
authors.initials: C
authors.lastname: Gourley
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gore
authors.forename: Stan B
authors.initials: SB
authors.lastname: Kaye
mesh_terms: D000328:Adult; D000367:Age Factors; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use*; D017671:Platinum Compounds / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D017239:Paclitaxel