Incidence of grade 3–4 adverse events, dose reduction, and treatment discontinuation in castration-resistant prostate cancer patients receiving PARP inhibitors: a meta-analysis

ABSTRACT

Background

PARP inhibitors (PARPi) have recently emerged as a new treatment option for several solid tumors, including metastatic castration-resistant prostate cancer (mCRPC). However, several grade 3–4 adverse events have been reported during PARPi administration, leading to limitations in treatment adherence.

Methods

Herein, we conducted a meta-analysis aimed at analyzing the incidence rate of commonly reported grade 3–4 adverse events, dose reduction, and treatment discontinuation in mCRPC patients treated with PARPi monotherapy.

Results

Incidence rate with 95% confidence intervals (CIs) of grade 3–4 toxicities, dose reduction, and treatment discontinuation were calculated. Six trials involving 752 mCRPC patients were available for the meta-analysis. According to our results, anemia was the most frequently observed grade 3–4 toxicity (24.1%), and dose reduction (26.9%) and treatment discontinuation (14.1%) were common events during PARPi treatment.

Conclusions

Clinicians should carefully consider these risks, especially taking into account that the use of PARPi in mCRPC patients is expected to rise in the near future.

KEYWORDS:

• Olaparib
• talazoparib
• rucaparib
• niraparib
• PARP
• mCRPC
• prostate cancer

Acknowledgments

We would like to thank all SEARCH! Team.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed speaker’s bureau from Janssen, Astellas, Pfizer and Dendreon. A reviewer on this manuscript has disclosed being on the advisory board for BMS, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, AstraZeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology and Infinity Pharmaceuticals; research support to their institution from Sanofi, AstraZeneca, Gilead, QED, Predicine and BMS; being on the steering committee of studies for BMS, Bavarian Nordic, Seattle Genetics, QED, G1 Therapeutics (all unpaid) and AstraZeneca, EMD Serono, Debiopharm (paid); being on the data safety monitoring committee for Mereo; spouse employment by Myriad; travel costs from BMS and AstraZeneca; writing/editor fees – Editor of Elsevier Practice update Bladder Cancer Center of Excellence; and speaker fees – Physicians Education Resource (PER), Onclive, Research to Practice, Medscape, Cancer Network and Masters Lecture Series (MLS). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

Conceptualization: A Rizzo and F Massari; methodology: A Rizzo and V Mollica; software: S Merler, F Massari and M Oderda; validation: all authors; formal analysis: A Rizzo; investigation: A Rizzo and F Massari; resources: all authors; data curation: all authors; writing – original draft preparation: A Rizzo, S Merler and F Massari; writing – review and editing: all authors; visualization: all authors.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This paper was not funded.