Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitors are a class of small-molecule drugs suppressing PARP enzymes activity, inducing the death of cells deficient in homologous recombination repair (HRR). HRR deficiency is common in tumor cells with BRCA gene mutation. Since their first clinical trial in 2003, PARP inhibitors have shown benefit in the treatment of HRR-deficient tumors. Recently, several randomized clinical trials (RCTs) have been conducted to investigate the potential benefit of administration of PARP inhibitors in cancer patients. However, the results remain controversial. To evaluate the efficiency and safety of PARP inhibitors in patients with cancer, we performed a comprehensive meta-analysis of RCTs. According to our study, PARP inhibitors could clearly improve progression-free survival (PFS), especially in patients with BRCA mutation. However, our study showed no significant difference in overall survival (OS) between the PARP inhibitors and controls, even in the BRCA mutation group. Little toxicity was reported in the rate of treatment correlated adverse events (AEs) in PARP inhibitor group compared with controls. In conclusion, PARP inhibitors do well in improving PFS with little toxicity, especially in patients with BRCA deficiency.
Highlights
The poly (ADP-ribose) polymerases (PARPs) are a family of enzymes comprising 18 members, and they play a vital role in maintaining the stability of the genome [1]
One article (OZA, 2013) [25] from EMBASE was partly overlapped with a previous publication (OZA 2015) [15], but it provided elaborated progression-free survival (PFS) data on the BRCA status, which was not mentioned in previous article, so it was included
Our meta-analysis showed no significant difference in overall survival rates between the PARP inhibitor and placebo arms in the overall population (HR, 0.92; 95% confidence interval (CI), 0.79–1.08) (Figure 3)
Summary
The poly (ADP-ribose) polymerases (PARPs) are a family of enzymes comprising 18 members, and they play a vital role in maintaining the stability of the genome [1]. PARP-1, which was first found ~50 years ago, is activated by DNA damage and plays a crucial role in the repair of single-strand breaks [2]. Another family member, PARP-2, has 69% structural similarity to PARP-1, and some of their functions overlap [3]. Evidence demonstrates that PARP is significantly increased in some cancer types, compared with adjacent non-tumorous tissues [4, 5]. This suggests that inhibition of PARP may provide a novel strategy for cancer therapy
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