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Can PARP Inhibitors Benefit Patients with Homologous Recombination Repair-Proficient Castration-Resistant Prostate

Susu Zhou¹, Devashish Desai², Noriko Kishi³

¹Division of Hematology and Oncology, Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, 13210, USA. zhous@upstate.edu.

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Summary

This summary is machine-generated.

Poly (ADP-ribose) polymerase inhibitors (PARPi) improve progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) regardless of homologous recombination repair (HRR) status. PARPi-based therapy shows clinical relevance in HRR-proficient mCRPC, warranting further research for patient selection.

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Area of Science:

Oncology
Genitourinary Cancers
Prostate Cancer Therapeutics

Background:

PARP inhibitors (PARPi) are established for HRR-deficient mCRPC.
Efficacy of PARPi in HRR-proficient mCRPC is not well-defined.

Purpose of the Study:

Evaluate PARPi efficacy in HRR-proficient mCRPC.
Compare efficacy between HRR-proficient and HRR-deficient mCRPC populations.

Main Methods:

Systematic literature search of clinical trials (PubMed, Embase, Cochrane, Web of Science, conference proceedings).
Single-arm and pairwise meta-analyses of PARPi efficacy in HRR-proficient and HRR-deficient mCRPC.
Subgroup analyses by treatment regimen.

Main Results:

Single-arm meta-analysis: PSA response 18% (HRR-proficient) vs 46% (HRR-deficient); 12-month PFS 42% vs 57%.
Pairwise meta-analysis: PARPi significantly improved PFS in both HRR-proficient (HR 0.69) and HRR-deficient (HR 0.60) mCRPC.
No significant differences in efficacy between HRR-proficient and HRR-deficient groups across analyses.

Conclusions:

PARPi improves PFS in mCRPC irrespective of HRR status.
PARPi-based therapy offers encouraging PFS benefits in HRR-proficient mCRPC.
Further biomarker research is needed to optimize PARPi selection and treatment strategies.