Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Preclinical studies and results of a phase 2 trial of abiraterone and olaparib suggest a combined antitumor effect when the poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor olaparib is combined with next-generation hormonal agent abiraterone to treat metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted a double-blind, phase 3 trial of abiraterone and olaparib versus abiraterone and placebo in patients with mCRPC in the first-line setting. Patients were enrolled regardless of homologous recombination repair gene mutation (HRRm) status. HRRm status was determined following enrollment by tumor tissue and circulating tumor DNA tests. Patients were randomly assigned (1:1) to receive abiraterone (1000 mg once daily) plus prednisone or prednisolone with either olaparib (300 mg twice daily) or placebo. The primary end point was imaging-based progression-free survival (ibPFS) by investigator assessment. Overall survival was among the secondary end points. RESULTS: At this planned primary analysis at the first data cutoff, median ibPFS was significantly longer in the abiraterone and olaparib arm than in the abiraterone and placebo arm (24.8 vs. 16.6 months; hazard ratio, 0.66; 95% confidence interval [CI], 0.54 to 0.81; P<0.001) and was consistent with blinded independent central review (hazard ratio, 0.61; 95% CI, 0.49 to 0.74). At this data cutoff, overall survival data were immature (28.6% maturity; hazard ratio, 0.86; 95% CI, 0.66 to 1.12; P=0.29). The safety profile of olaparib and abiraterone was consistent with the known safety profiles of the individual drugs. The most common adverse events in the abiraterone and olaparib arm were anemia, fatigue/asthenia, and nausea. CONCLUSIONS: At primary analysis at this first data cutoff, abiraterone combined with olaparib significantly prolonged ibPFS compared with abiraterone and placebo as first-line treatment for patients with mCRPC enrolled irrespective of HRRm status. (Funded by AstraZeneca and Merck Sharp & Dohme, LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; ClinicalTrials.gov number, NCT03732820.)

Association of common variations of 8q24 with the risk of prostate cancer in Koreans and a review of the Asian population.

UNLABELLED: What's known on the subject? and What does the study add? The association between subjects with the genetic variation of 8q24 and the risk of development of prostate cancer in Korean men was found. As a result of haplotype analysis, [AGC] and [CTA] carriers showed a significant association with prostate cancer risk. This is clinically meaningful as an initial study on genetic susceptibility to prostate cancer in Korean men and the first report of 8q24 haplotypes in an Asian population. OBJECTIVE: To determine the association between genetic variation of 8q24 with prostate cancer risk in Korean men. PATIENTS AND METHODS: With a hospital-based case-control study design, we enrolled 194 patients with prostate cancer and 169 healthy controls from visitors for cancer screening. DNA samples were obtained from peripheral blood for the analysis of single nucleotide polymorphisms (SNPs). Three SNPs of 8q24, including rs16901979, rs6983267, and rs1447295, were genotyped on cases and controls. RESULTS: The subjects with the rs1447295 CA or AA genotype had a higher risk of prostate cancer than the CC genotype. The A allele at SNP rs1447295 was associated with the incidence of prostate cancer. The rs16901979 CA genotype carriers had a higher risk of prostate cancer than the CC genotype. Individuals with the [AGC] and [CTA] haplotypes had a significantly increased risk of prostate cancer compared with the [CTC] haplotype ([AGC] with adjusted odds ratio [OR] 1.79; 95% confidence interval [CI] 1.09-2.96; P = 0.022; [CTA] with adjusted OR 5.17; 95% CI 2.40-11.15; P < 0.001). CONCLUSIONS: The genetic variation of 8q24 is associated with the risk of prostate cancer in Korean men. Individuals with the [AGC] and [CTA] haplotypes had a significant association with prostate cancer risk.