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 language | English |
|---|---|
| Article number | e000361 |
| Journal | ESMO Open |
| Volume | 3 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jun 1 2018 |
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Keywords
- BRCA mutation
- chemotherapy
- metastatic breast cancer
- PARP inhibitors
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Single-agent PARP inhibitors for the treatment of patients with BRCA -mutated HER2-negative metastatic breast cancer : A systematic review and meta-analysis. / Poggio, Francesca; Bruzzone, Marco; Ceppi, Marcello; Conte, Benedetta; Martel, Samuel; Maurer, Christian; Tagliamento, Marco; Viglietti, Giulia; Del Mastro, Lucia; De Azambuja, Evandro; Lambertini, Matteo.
In: ESMO Open, Vol. 3, No. 4, e000361, 01.06.2018.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Single-agent PARP inhibitors for the treatment of patients with BRCA -mutated HER2-negative metastatic breast cancer
T2 - A systematic review and meta-analysis
AU - Poggio, Francesca
AU - Bruzzone, Marco
AU - Ceppi, Marcello
AU - Conte, Benedetta
AU - Martel, Samuel
AU - Maurer, Christian
AU - Tagliamento, Marco
AU - Viglietti, Giulia
AU - Del Mastro, Lucia
AU - De Azambuja, Evandro
AU - Lambertini, Matteo
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
KW - BRCA mutation
KW - chemotherapy
KW - metastatic breast cancer
KW - PARP inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85050684237&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050684237&partnerID=8YFLogxK
U2 - 10.1136/esmoopen-2018-000361
DO - 10.1136/esmoopen-2018-000361
M3 - Review article
AN - SCOPUS:85050684237
VL - 3
JO - ESMO Open
JF - ESMO Open
SN - 2059-7029
IS - 4
M1 - e000361
ER -