A Case of Metastatic Castration-Resistant Prostate Cancer With RAD54L Mutation Responding to Niraparib

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• Prostate cancers can harbor alterations in homologous recombination repair (HRR) genes.
• Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 mutations.
• Efficacy of PARP inhibitors for other HRR gene alterations remains unclear.

Purpose of the Study:

• To evaluate the efficacy of niraparib in a patient with mCRPC and a RAD54L gene mutation.
• To assess the role of targeted therapy based on comprehensive genomic profiling.

Main Methods:

• A patient with mCRPC underwent FoundationOne CDx testing, revealing a pathogenic RAD54L variant.
• The patient was enrolled in the BELIEVE Trial and treated with niraparib.
• Treatment response was monitored via PSA levels and metastatic lesion size.

Main Results:

• Niraparib treatment initially led to a significant decrease in PSA and reduction of metastatic lesions.
• The patient experienced disease progression with rising PSA and enlarged metastatic lesions after 25 weeks.
• Treatment with niraparib was discontinued due to disease progression.

Conclusions:

• Niraparib demonstrated initial efficacy in a patient with mCRPC harboring a RAD54L gene mutation.
• The case highlights the potential utility of PARP inhibitors beyond BRCA mutations in prostate cancer.
• Further investigation is warranted to establish the role of niraparib in HRR-mutated mCRPC.