Implications of BRCA1 and BRCA2 mutations for the efficacy of paclitaxel monotherapy in advanced ovarian cancer

Eur J Cancer. 2013 Apr;49(6):1246-53. doi: 10.1016/j.ejca.2012.11.016. Epub 2012 Dec 19.


Introduction: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Mutation*
  • Neoplasm Staging
  • Organoplatinum Compounds / therapeutic use
  • Outcome Assessment, Health Care / statistics & numerical data
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / therapeutic use*
  • Platinum Compounds / therapeutic use
  • Proportional Hazards Models
  • Remission Induction
  • Retrospective Studies
  • Time Factors


  • Antineoplastic Agents, Phytogenic
  • BRCA1 Protein
  • BRCA2 Protein
  • Organoplatinum Compounds
  • Platinum Compounds
  • Paclitaxel