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Comparison of Adverse Events Between PARP Inhibitors in Patients with Epithelial Ovarian Cancer: A Nationwide Propensity Score Matched Cohort Study

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Abstract

Background

Despite improvement in progression-free survival (PFS) with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) as maintenance treatment for patients with epithelial ovarian cancer (EOC), a comparative analysis of clinical events of interest (CEIs) of different PARPi is scarce.

Objective

This study aimed to compare the safety of different PARPi in patients with EOC.

Patients and Methods

Through analyzing the Korean National Health Insurance Service from January 2009 to January 2022, this study involved BRCA-mutated, platinum-sensitive patients with EOC treated with olaparib (tablet), niraparib, and olaparib (capsule) as first-line or second-line maintenance treatment. CEIs were identified using International Statistical Classification of Diseases (ICD) 9/10 codes, with additional outcomes being dose modification and persistence.

Results

In the first-line maintenance treatment [118 niraparib, 104 olaparib (tablet) patients], no significant differences were noted in CEIs, dose reduction, or 6-month discontinuation rate. For second-line maintenance treatment [303 niraparib, 126 olaparib (tablet), and 675 olaparib (capsule) patients], niraparib was associated with a higher risk of hematologic CEIs, particularly anemia, compared with olaparib (tablet) (0.51 [0.26–0.98] and 0.09 [0.01–0.74], respectively), and higher rate of discontinuation rate at 6 months. Of note, patients over 60 years old showed an increased risk of CEIs with niraparib, as indicated by the hazard ratio divergence in restricted cubic spline plots.

Conclusions

No differences were observed among the PARPi during first-line maintenance treatment. However, in the second-line maintenance treatment, significant differences were observed in the risk of experiencing CEIs, dose alteration possibilities, and discontinuation of PARPi between niraparib and olaparib (tablets). Moreover, our findings suggest that an age of 60 years may be a critical factor in selecting PARPi to reduce CEI incidence.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, 01757, Republic of Korea

    Gwan Hee Han

  2. Department of Statistics, College of Natural Science, University of Seoul, Seoul, 02504, Republic of Korea

    Hae-Rim Kim

  3. Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 06299, Republic of Korea

    Hee Yun

  4. Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, 03772, Republic of Korea

    Jae-Hoon Kim & Hanbyoul Cho

  5. Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

    Jae-Hoon Kim & Hanbyoul Cho

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Correspondence to Hanbyoul Cho.

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Funding

This study was supported by a National Research Foundation of Korea (NRF) grant, funded by the Korean government (MIST; grant no. NRF-2020R1A2C2004782, and NRF-2022R1F1A1071806). This research was supported by the Bio and Medical Technology Development Program of the NRF, funded by the Korean government (MIST; grant no. NRF-2017M3A9B8069610). This study was also supported by a faculty research grant from the Yonsei University College of Medicine (grant no. 6-2020-0226). This work was supported by the 23 Inje University research grant (grant no. 20230084).

Conflict of interest

Gwan Hee Han, Hae-Rim Kim, Hee Yun, Jae-Hoon Kim, and Hanbyoul Cho declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Ethics approval

The study design adhered to the ethical guidelines of the 1975 Declaration of Helsinki and received approval from the Institutional Review Board (IRB) of the Gangnam Severance Hospital (IRB No. 3-2022-0330).

Consent to participate

Informed consent was waived from the IRB due to the retrospective design.

Consent to publish

Not applicable.

Data availability

The datasets generated during and / or analysed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Author contributions

Conceptualization was carried out by Hanbyoul Cho; formal analysis was performed by Gwan Hee Han; investigation was performed by Hae-Rim Kim, Hee Yun, and Gwan Hee Han; writing—original draft preparation was carried out by Gwan Hee Han; and writing—review and editing was carried out by Hanbyoul Cho and Jae-Hoon Kim.

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Han, G.H., Kim, HR., Yun, H. et al. Comparison of Adverse Events Between PARP Inhibitors in Patients with Epithelial Ovarian Cancer: A Nationwide Propensity Score Matched Cohort Study. Targ Oncol 19, 251–262 (2024). https://doi.org/10.1007/s11523-024-01037-0

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