Efficacy and Safety of PARP Inhibitors in Advanced or Metastatic Triple-negative Breast Cancer: A Systematic Review and Meta-analysis

Abstract BackgroundPoly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in metastatic triple-negative breast cancers (TNBC). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of this drug in patients with advanced or metastatic TNBC.MethodsOn August 2020, we searched all published phase II/III clinical studies of PARP inhibitors in advanced/metastatic TNBC patients. Data were extracted independently by two authors and analyzed using Review Manager software version 5.3. End points included overall response rate (ORR), progression-free survival (PFS) and adverse events.ResultsTen clinical trials were identified, with a total of 1495 patients included. Pooled analyses showed that the addition of PARP inhibitors could provide a significant improvement of ORR (risk ratio [RR]=2.00, 95% confidence interval [CI]: 1.14–3.50, p=0.02) and PFS (hazard ratio [HR]=0.68, 95 %Cl: 0.59-0.77, p<0.0001) compared to chemotherapy in the whole population. In subgroup analysis, BRCA mutated patients have a higher objective response to PARP inhibitor, with a RR of 2.85 (95%CI: 1.34–6.06, p=0.007) compared to BRCA wild-type patients. However, no significant differences in ORR were observed between homologous recombination deficiency (HRD) positive and non-HRD subgroup (RR=1.82, 95%CI: 0.81–4.08, p=0.14). Hematologic toxicities were common adverse events of PARP inhibitors.ConclusionsPARP inhibitors are an effective option for the treatment of advanced or metastatic TNBC patients. BRCA mutated patients could derive more benefits from PARP inhibitors when compared to BRCA wild-type patients. In clinical application, hematological toxicity related to PARP inhibitors should be monitored regularly.