Risk of secondary hematologic malignancies and tolerability in patients with ovarian cancer treated with PARP inhibitors: A systematic review and meta-analysis of four phase III randomized controlled trials.

Authors

Kyaw Zin Thein

Kyaw Zin Thein

University of Texas MD Anderson Cancer Center, Houston, TX

Kyaw Zin Thein , Somedeb Ball , Anita Sultan , Sriman Swarup , Myo Zaw , Thura WIN Htut , Pwint Phyu Hlaing , Yin Mon Myat , Rachana Yendala , Nicholas C. D'Cunha , Donald Quick , Lukman Aderoju Tijani

Organizations

University of Texas MD Anderson Cancer Center, Houston, TX, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, Texas Tech University Health Sciences Center, Lubbock, TX, Brooklyn Hospital Center, Brooklyn, NY, Colchester Hospital University NHS Foundation Trust, Essex, United Kingdom, University College Dublin, Belfield, Ireland, Texas Tech University Health Sciences, Lubbock, TX, Texas Tech University Health Science Center, Lubbock, TX, Joe Arrington Cancer Research and Treatment Center, Lubbock, TX, Thomas Jefferson University Hospital, Lubbock, TX

Research Funding

Other

Background: Poly adenosine diphosphate ribose polymerase (PARP) inhibitors have shown to improve survival in ovarian cancer (OC) through synthetic lethality with potentiation of double-strand breaks in tumor cells. Yet, there are concerns of secondary hematologic malignancies (SHM) and notable adverse events (AE) leading to treatment discontinuation (TD), interruption (TI), or dose reduction (DR). Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through January 2019 were queried. Phase 3 RCTs utilizing PARP inhibitors maintenance in OC were eligible. 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: A total of 1792 patients from four phase III RCTs were included. The study arm used olaparib or niraparib or rucaparib while the control arm utilized placebo. Almost all patients in the SOLO-2 & -1 trials had a gBRCA mutation, while there were patients with and without the said mutation in the other two studies. The SHM incidence was 1.25% in PARP inhibitors group vs 0.83% in control group (RR, 1.15; 95% CI: 0.41–3.22, p = 0.79). TI due to AE was 59.71% in study group versus 11.39% in control arm (RR, 4.94; 95% CI: 2.44 – 9.96, P < 0.001). DR was reported in 47.73% in PARP inhibitors arm versus 6.86% in control group (RR, 7.73; 95% CI: 4.17 – 14.31, P < 0.001). TD rate was 10.97% higher in study group compared to control arm (RR, 6.63; 95% CI: 3.55 – 11.31, P < 0.001). Conclusions: The risk of SHM was not significantly increased in PARP inhibitors group. However, patients on PAPR inhibitors arm experienced significant drop outs due to AE, despite showing significant improvement in PFS in studies. Proper supportive care may enhance compliance.

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Symptoms and Survivorship: Publication Only

Track

Symptom Science and Palliative Care

Sub Track

Health Promotion/Behaviors

Citation

J Clin Oncol 37, 2019 (suppl; abstr e23056)

DOI

10.1200/JCO.2019.37.15_suppl.e23056

Abstract #

e23056

Abstract Disclosures

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