(Funded by AstraZeneca and Merck Sharp & Dohme PROfound number, NCT02987543.) Introduction In men with metastatic castration-resistant prostate cancer who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair, olaparib was associated with longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. Anemia and nausea were the main toxic effects in patients who received olaparib. A significant benefit for olaparib was also seen for imaging-based progression-free survival in the overall population (cohorts A and B). The median overall survival in cohort A was 18.5 months in the olaparib group and 15.1 months in the control group 81% of the patients in the control group who had progression crossed over to receive olaparib. 3.6 months hazard ratio for progression or death, 0.34 95% confidence interval, 0.25 to 0.47 P<0.001) a significant benefit was also observed with respect to the confirmed objective response rate and the time to pain progression. In cohort A, imaging-based progression-free survival was significantly longer in the olaparib group than in the control group (median, 7.4 months vs. The primary end point was imaging-based progression-free survival in cohort A according to blinded independent central review. Patients were randomly assigned (in a 2:1 ratio) to receive olaparib or the physician’s choice of enzalutamide or abiraterone (control). Cohort A (245 patients) had at least one alteration in BRCA1, BRCA2, or ATM cohort B (142 patients) had alterations in any of 12 other prespecified genes, prospectively and centrally determined from tumor tissue. All the men had a qualifying alteration in prespecified genes with a direct or indirect role in homologous recombination repair.
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We conducted a randomized, open-label, phase 3 trial evaluating the PARP inhibitor olaparib in men with metastatic castration-resistant prostate cancer who had disease progression while receiving a new hormonal agent (e.g., enzalutamide or abiraterone). Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate–ribose) polymerase (PARP) inhibition in patients with prostate and other cancers. The most trusted, influential source of new medical knowledge and clinical best practices in the world.
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The defense says that this, along with spiraling depression, job and relationship unhappiness, prompted Clarkson to commit suicide upon entering Spector's foyer. I hate this town and I don't want to be here anymore," said Clarkson, according to testimony of her friend, Punkin Irene Elizabeth Laughlin. "Michael Bay just dissed me, didn't know who I was. But when she approached him at a music industry party, he blew her off. Years earlier, Clarkson appeared in a Mercedes Benz commercial directed by Bay, and the struggling actress was hoping that he would remember her and help her find acting work. Friends of slain actress Lana Clarkson, who was found shot dead in Spector's house, took the stand today and testified that in the days before her death, Clarkson was distraught over a run-in she'd had with Bay. Today's testimony at the Phil Spector murder trial took a strange turn to "Transformers" director Michael Bay.
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