A systematic review and meta- analysis of randomized controlled trials to evaluate the risk of hematological toxicities in patients with cancer treated with poly adenosine diphosphate ribose polymerase (PARP) inhibitors.

Abstract

217 Background: Poly adenosine diphosphate ribose polymerase (PARP) inhibitors have shown to benefit in DNA repair-deficient tumors by enhancing synthetic lethality in cancer cells and are currently employed in many solid tumors. Nevertheless, the risk of hematological toxicities remains significant. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of hematological toxicities. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018. Phase III RCTs that mention hematological toxicities as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Seven phase III RCTs with a total of 3,188 patients with breast, ovarian and gastric cancer were eligible. Studies compared olaparib or niraparib or rucaparib versus placebo, olaparib vs single agent chemotherapy, iniparib + gemcitabine / carboplatin (GC) versus GC, veliparib + C versus C and olaparib + paclitaxel vs paclitaxel. The RR of all-grade side effects were as follows: anemia, 2.38 (95% CI: 1.42 – 4.00, p = 0.001); thrombocytopenia, 2.96 (95% CI: 1.37 – 6.40, p = 0.006); neutropenia, 1.47 (95% CI: 1.06 – 2.05, p = 0.02); and leukopenia, 1.08 (95% CI: 0.77 – 1.50, p = 0.63). The RR of high-grade adverse effects were as follows: anemia, 3.63 (95% CI: 1.53 – 8.57, p = 0.003); thrombocytopenia, 2.65 (95% CI: 0.89 – 7.85, p = 0.07); neutropenia, 1.27 (95% CI: 0.87 – 1.86, p = 0.21); and leukopenia, 1.20 (95% CI: 0.90 – 1.58, p = 0.19). Conclusions: Our meta-analysis demonstrated that patients on PARP inhibitors experienced a significant increase in the risk of all grades of anemia with a relative risk of 3.63 for grade 3 and 4 anemia, along with any-grade thrombocytopenia and neutropenia. Proper supportive care is essential, and it will ultimately reduce drug dosing inconsistencies and financial burden among patients undergoing treatment.