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.

Authors

null

Anita Sultan

Texas Tech University Health Sciences Center, Lubbock, TX

Anita Sultan, Sriman Swarup, Myo Zaw, Myat M. Han, Yin Mon Myat, Htay Htay Aung, Myet Mon Mon Zin, Kalpana Panigrahi, Kyaw Zin Thein

Organizations

Texas Tech University Health Sciences Center, Lubbock, TX, Brooklyn Hospital Center, Brooklyn, NY, University of Texas MD Anderson Cancer Center, Houston, TX, University College Dublin, Belfield, Ireland, Kingsbrook Jewish Medical Center, Brooklyn, NY

Research Funding

Other

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.

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Abstract Details

Meeting

2018 Palliative and Supportive Care in Oncology Symposium

Session Type

Poster Session

Session Title

Poster Session B: Advance Care Planning; Caregiver Support; Coordination and Continuity of Care; End-of-Life Care; Models of Care; Survivorship; and Symptom Biology, Assessment and Management

Track

Advance Care Planning,End-of-Life Care,Survivorship,Coordination and Continuity of Care,Symptom Biology, Assessment, and Management,Models of Care,Caregiver Support

Sub Track

Symptom Biology, Assessment, and Management

Citation

J Clin Oncol 36, 2018 (suppl 34; abstr 217)

DOI

10.1200/JCO.2018.36.34_suppl.217

Abstract #

217

Poster Bd #

G3

Abstract Disclosures