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Single-agent PARP inhibitors for the treatment of patients with BRCA-mutated HER2-negative metastatic breast cancer: a systematic review and meta-analysis
  1. Francesca Poggio1,2,
  2. Marco Bruzzone3,
  3. Marcello Ceppi3,
  4. Benedetta Conte2,
  5. Samuel Martel4,
  6. Christian Maurer5,
  7. Marco Tagliamento2,
  8. Giulia Viglietti6,
  9. Lucia Del Mastro7,
  10. Evandro de Azambuja1,
  11. Matteo Lambertini1,6
  1. 1 Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Bruxelles, Belgium
  2. 2 Department of Medical Oncology, Oncologia Medica 2, Ospedale Policlinico San Martino, Genova, Italy
  3. 3 Unit of Clinical Epidemiology, Ospedale Policlinico San Martino, Genova, Italy
  4. 4 Department of Hemato-Oncology, CISSS Montérégie-Centre/Hôpital Charles-Le Moyne, centre affilié de l’Université de Sherbrooke, Quebec, Canada
  5. 5 Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany
  6. 6 Breast Cancer Translational Research Laboratory, Institute Jules Bordet, Université Libre de Bruxelles (U.L.B.), Bruxelles, Belgium
  7. 7 Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, Ospedale Policlinico San Martino, Department of Internal Medicine and Medical Specialties (DIMI), University of Genova, Genova, Italy
  1. Correspondence to Dr Matteo Lambertini; matteo.lambertini85{at}gmail.com

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.

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

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors All the authors make substantial contributions to conception and design, and/or acquisition of data, and/or analysis and interpretation of data, giving final approval of the version to be submitted.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests LDM received personal fees from Novartis Pharma AG, Roche-Genentech, Ipsen, Astrazeneca, Takeda, Eli Lilly outside the submitted work. EdA received honoraria from Roche-Genentech, research grant from Roche-Genentech (to the institution) and travel grants from Roche-Genentech and GlaxoSmithKline outside the submitted work. ML served as a consultant for Teva outside the submitted work.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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