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

David S. P. Tan, Timothy A. Yap, Margaret Hutka, Patricia Roxburgh, Jooern Ang, Susana Banerjee, Ewa Grzybowska, Charlie Gourley, Martin E. Gore, Stan B. Kaye*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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. (C) 2012 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1246-1253
Number of pages8
JournalEuropean Journal of Cancer
Volume49
Issue number6
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Ovarian cancer
  • Response
  • BRCA2
  • IMPROVED SURVIVAL
  • INACTIVATION
  • CHEMOSENSITIVITY
  • BRCA1
  • CARCINOMA
  • WOMEN
  • Resistance
  • CELL-LINE
  • Paclitaxel
  • CHEMOTHERAPY
  • RESISTANCE
  • CISPLATIN
  • Taxane
  • INHIBITION

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