Poly(ADP-Ribose) Polymerase Inhibitors (PARPi) for patients (pts) with locally advanced or metastatic breast cancer (BC): A meta-analysis.
Year: 2018
Type: conference-abstract
Abstract: 1076 Background: We performed a quantitative meta-analysis of randomized clinical trials of PARPi in pts with BC. Methods: 2 registries (ClinicalTrials.gov, WHO ICTRP) and 4 electronic databases (CBCG SR, CENTRAL, Medline, EMBASE) were searched from 2008 to 1/2018 for randomized clinical trials (RCTs) of PARPi therapy vs. control in BC. RCTs that reported overall survival (OS) or progression-free survival (PFS) were included. Pooled hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using a fixed effects model. Results: We identified 418 citations, of which 2 RCTs with a pooled sample size of n = 733 were included. There was a low/moderate risk of bias in both RCTs (Table). Both RCTs compared a PARPi to physician's choice of chemotherapy in pts with germline BRCA mutated HER2-negative BC in first or later line setting, with PFS as the primary outcome. The pooled analysis of PFS showed a statistically significant improvement with PARPi therapy, with an HR 0.56 (95% CI 0.45-0.68). The pooled analysis of OS did not show a statistically significant improvement, with an HR of 0.82 (95% CI 0.64-1.05). There was an acceptable safety profile with PARP therapy in both RCTs, with a grade ≥ 3 adverse event rate of 25.5% and 36.6% in the 2 RCTs respectively. Conclusions: The use of PARPi in pts with germline BRCA mutated HER2-negative BC offers a PFS benefit compared to physician's choice of chemotherapy in the first or later line setting, with an acceptable adverse events rate. Lack of OS benefit may be explained by availability of further lines of therapy, relative immaturity of the trials and not being powered to assess OS. This systematic review is part of a planned Cochrane Breast Cancer Group protocol. Sequence generation Allocation concealment Blinding pts & staff Blinding outcome assessment Incomplete outcome data Selective reporting Intention to treat Robson et al, 2017 Centralized random number generator Allocation concealed Not blinded Blinded. Primary outcome reported 98% of pts No selective reporting Yes Risk L L H L L L L Litton et al, 2017 Not described Not described Not blinded Blinded Primary outcome reported 96% of pts No selective reporting Yes Risk H H H L L L L H: High; L: Low
Source: Journal of Clinical Oncology
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2805290770