Evaluation of efficacy and safety of PARP inhibitors in breast cancer: A systematic review and meta-analysis

Abstract

Background: Many breast cancer clinical trials with PARPi have been completed or are currently carried out, either by monotherapy or combined with chemotherapy. We aim to assess the efficacy and safety of PARPi in breast cancer patients as compared to chemotherapy.

Methods: A comprehensive literature search of PubMed, EMBASE, CENTRAL, conference meetings and clinical trial registry was performed. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR). The secondary outcome was safety profile. The comparative effects were measured using hazard ratio (HR) or relative risk (RR) with 95% confidence interval. Subgroup analyses were conducted based on types of intervention and baseline characteristics of patients.

Results: Six RCTs (n = 1953) were included. Two RCTs were recognized as high risk. PARPi was associated with an improved PFS (HR, 0.65; 95% CI, 0.56-0.74), OS (HR, 0.86; 95% CI, 0.73-1.01), and a higher ORR (RR, 1.38; 95% CI, 1.05-1.82). PARPi, however, significantly increased risk of grade 3-4 thrombocytopenia (RR, 1.63; 95% CI, 1.06-2.52). Monotherapy was observed with lower risk of disease progression and higher ORR rate than combination therapy, 0.56 to 0.65 and 2.21 to 1.05, respectively. For patients without prior platinum treatment, PARPi significantly improved PFS (HR, 0.64; 95% CI, 0.52-0.79).

Conclusions: PARPi was observed with a significantly improved efficacy in aspects of PFS and ORR, but also higher risk of grade 3-4 thrombocytopenia as compared to chemotherapy. PARPi was a better choice for patients who had not received previous platinum treatment.

Keywords: Breast neoplasms; Meta-analysis; Poly-ADP-Ribose polymerase.

Fig. 1

Flow chart of study selection.

Fig. 2

Comparative effects of PARP inhibitors versus chemotherapy on progression-free survival of breast cancer patients. Results were presented as individual and pooled HR with 95% CI.

Fig. 3

Comparative effects of PARP inhibitors versus chemotherapy on overall survival of breast cancer patients. Results were presented as individual and pooled HR with 95% CI.

Fig. 4

Comparative effects of PARP inhibitors versus chemotherapy on overall response rate of breast cancer patients. Results were presented as individual and pooled HR with 95% CI. PARP inhibitors versus chemotherapy: safety.