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In heavily pretreated patients with pathogenic BRCA2 variants, PARP inhibitors showed a significant PSA response rate and a better progression-free survival
A new study published on JCO Precision Oncology describes PARP inhibitors outcomes in patients with advanced prostate cancer bearing alterations in homologous recombination repair (HRR) genes in a real-world setting, emphasizing the importance of determining pathogenicity and origin of HRR alterations to better inform clinical treatment decisions: PARP inhibitors indeed showed a significant PSA response rate and progression-free survival in patients with pathogenic BRCA2 variants.
Authors reviewed the US Department of Veterans Affairs’ National Precision Oncology Program’s database to identify patients with advanced prostate cancer who underwent somatic DNA sequencing and were prescribed a PARP inhibitor; 48 patients with a total of 67 HRR gene variants were analyzed. The rate of those achieving a 30% decrease in PSA and composite progression-free survival were compared between patients bearing pathogenic variants of BRCA2 and patients without these variants. The median progression-free survival was 4 months, and PSA30 was 25.6% for all 43 evaluable patients; patients with pathogenic BRCA2 variants had higher PSA30 (69.2% versus 4.0%) and longer progression-free survival (7.2 versus 2.8 months) than those without. «Approximately one half of patients with prostate cancer are prescribed PARP inhibitors without harboring a pathogenic/likely pathogenic HRR gene variant», authors say. «Patients bearing pathogenic/likely pathogenic BRCA2 mutations more frequently have longer progression-free survival and are more likely to achieve a significant PSA reduction compared with others receiving PARP inhibitors. This work emphasizes the importance of determining pathogenicity and origin of HRR alterations to better inform clinical treatment decisions and highlights the need for improving oncologist education and health informatics tools to increase conformance of practice to recommended precision oncology care of men with metastatic prostate cancer».