Single-agent PARP inhibitors for the treatment of patients with BRCA -mutated HER2-negative metastatic breast cancer: A systematic review and meta-analysis

Francesca Poggio, Marco Bruzzone, Marcello Ceppi, Benedetta Conte, Samuel Martel, Christian Maurer, Marco Tagliamento, Giulia Viglietti, Lucia Del Mastro, Evandro De Azambuja, Matteo Lambertini

Research output: Contribution to journalReview article

Abstract

Single-agent poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been approved as the first targeted therapy available for patients with BRCA-mutated HER2-negative metastatic breast cancer. This meta-analysis aimed to better evaluate activity, efficacy and safety of single-agent PARPi in this population. A systematic search of Medline, Embase and conference proceedings up to 31 January 2018 was conducted to identify randomised controlled trials (RCTs) investigating single-agent PARPi versus monochemotherapy in patients with BRCA-mutated HER2-negative metastatic breast cancer. Using the random-effect model, we calculated summary risk estimates (pooled HR and OR with 95% CI) for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), any grade and grade 3-4 adverse events (AEs), treatment discontinuation rate and time to deterioration in quality of life (QoL). Two RCTs (n=733) were included. As compared with monochemotherapy, single-agent PARPi significantly improved PFS (HR 0.56(95% CI 0.45 to 0.70)) and ORR (OR 4.15 (95% CI 2.82 to 6.10)), with no difference in OS (HR 0.82 (95% CI 0.64 to 1.05)). Single-agent PARPi significantly increased risk of anaemia and any grade headache, but reduced risk of neutropenia and any grade palmar-plantar erythrodysesthesia syndrome as compared with monochemotherapy. No significant differences in other AEs and treatment discontinuation rate were observed. Patients treated with PARPi experienced a significant delayed time to QoL deterioration (HR 0.40 (95% CI 0.29 to 0.54)). Single-agent PARPi showed to be an effective, well tolerated and useful treatment in maintaining QoL of patients with BRCA-mutated HER2-negative metastatic breast cancer.

Original languageEnglish
Article numbere000361
JournalESMO Open
Volume3
Issue number4
DOIs
Publication statusPublished - Jun 1 2018

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Keywords

  • BRCA mutation
  • chemotherapy
  • metastatic breast cancer
  • PARP inhibitors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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