Olaparib (Lynparza) has received an FDA breakthrough therapy designation as a treatment for patients with BRCA1/2
-mutated metastatic castration-resistant prostate cancer (mCRPC) in those who have received a prior taxane-based chemotherapy and at least either hormonal agent enzalutamide (Xtandi) or abiraterone acetate (Zytiga).
Using NGS, the researchers discovered that 16 of 49 (33%) patients had homozygous deletions, deleterious mutations, or both in DNA-repair genes. Fourteen of these 16 (88%) patients (labeled as “biomarker-positive”) responded to olaparib.
Of these 14 patients, 7 harbored BRCA2
mutations, 5 had ATM
aberrations, and 2 had ATM
mutations with no germline events. Homozygous somatic deletions of BRCA1
occurred with FANCA
deletion in 3 patients, while a somatic frameshift mutation in PALB2
was also detected in a patient with a heterozygous PALB2
deletion. Moreover, biallelic somatic aberrations in histone deacetylase 2 (HDAC2
) were identified in 1 patient.
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