Efficacy of Radium-223 in Bone-Metastatic Castration-Resistant Prostate Cancer With and Without Homologous Repair Gene Defects

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Somatic tumor and germline DNA testing are becoming more meaningful in the management of patients with advanced prostate cancer. This study evaluated the potential impact of germline or somatic homologous recombination deficiency (HRD) mutations on radium-223 efficacy in metastatic castrate-resistant prostate cancer (mCRPC) with bone metastasis. A total of 190 mCRPC patients for whom germline and/or somatic DNA sequencing data were available were reviewed. Of these patients, 28 had received standard-of-care radium-223 at a single center between 2013 and 2018. The authors found 36% of radium-223 patients had an HRD mutation (BRCA2 was the most prevalent). HRD-positive patients showed greater alkaline phosphatase response and a trend toward longer overall survival (median, 36.9 vs 19.0 months) compared with HRD-negative patients.

Based on these data, the authors suggest that patients who have inherited or acquired DNA repair gene mutations derive greater benefit from radium-223 compared with patients without these mutations.

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