Poggio, Francesca ORCID: 0000-0002-4518-2827, Bruzzone, Marco ORCID: 0000-0002-8821-4542, Ceppi, Marcello ORCID: 0000-0002-8177-8003, Conte, Benedetta, Martel, Samuel, Maurer, Christian, Tagliamento, Marco ORCID: 0000-0001-7461-023X, Viglietti, Giulia, Del Mastro, Lucia ORCID: 0000-0002-9546-5841, de Azambuja, Evandro ORCID: 0000-0001-9501-4509 and Lambertini, Matteo ORCID: 0000-0003-1797-5296 (2018). Single-agent PARP inhibitors for the treatment of patients with BRCA-mutated HER2-negative metastatic breast cancer: a systematic review and meta-analysis. ESMO Open, 3 (4). LONDON: BMJ PUBLISHING GROUP. ISSN 2059-7029

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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 HER2negative metastatic breast cancer.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Poggio, FrancescaUNSPECIFIEDorcid.org/0000-0002-4518-2827UNSPECIFIED
Bruzzone, MarcoUNSPECIFIEDorcid.org/0000-0002-8821-4542UNSPECIFIED
Ceppi, MarcelloUNSPECIFIEDorcid.org/0000-0002-8177-8003UNSPECIFIED
Conte, BenedettaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martel, SamuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maurer, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tagliamento, MarcoUNSPECIFIEDorcid.org/0000-0001-7461-023XUNSPECIFIED
Viglietti, GiuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Del Mastro, LuciaUNSPECIFIEDorcid.org/0000-0002-9546-5841UNSPECIFIED
de Azambuja, EvandroUNSPECIFIEDorcid.org/0000-0001-9501-4509UNSPECIFIED
Lambertini, MatteoUNSPECIFIEDorcid.org/0000-0003-1797-5296UNSPECIFIED
URN: urn:nbn:de:hbz:38-188656
DOI: 10.1136/esmoopen-2018-000361
Journal or Publication Title: ESMO Open
Volume: 3
Number: 4
Date: 2018
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2059-7029
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TEMOZOLOMIDE; VELIPARIBMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18865

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