Olaparib for Metastatic Castration-Resistant Prostate Cancer
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Résumé
BACKGROUND: 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. METHODS: ; cohort B (142 patients) had alterations in any of 12 other prespecified genes, prospectively and centrally determined from tumor tissue. Patients were randomly assigned (in a 2:1 ratio) to receive olaparib or the physician's choice of enzalutamide or abiraterone (control). The primary end point was imaging-based progression-free survival in cohort A according to blinded independent central review. RESULTS: 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. 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. 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. A significant benefit for olaparib was also seen for imaging-based progression-free survival in the overall population (cohorts A and B). Anemia and nausea were the main toxic effects in patients who received olaparib. CONCLUSIONS: 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. (Funded by AstraZeneca and Merck Sharp & Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).
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La notice
- Revue
- New England Journal of Medicine
- Thématique
- Prostate Cancer Treatment and Research
- Domaine
- Medicine
- Établissements canadiens
- BC Cancer AgencyCentre Hospitalier de l’Université de Montréal
- Organismes subventionnaires
- Daiichi Sankyo EuropeJanssen PharmaceuticalsJanssen BiotechFoundation MedicinePharmacyclicsGenentechAstellas Pharma EuropeTulane UniversityEisaiAstellas PharmaMerck Sharp and DohmeRadboud Universitair Medisch CentrumEMD SeronoRadboud UniversiteitAstraZenecaInvitaeMassachusetts Medical SocietyBayer HealthCareSanofiExelixisPfizerNorthwestern UniversityIpsenClovis OncologyF. Hoffmann-La RocheEli Lilly and CompanyBristol-Myers Squibb
- Mots-clés
- OlaparibPoly ADP ribose polymeraseProstate cancerHomologous recombinationPARP inhibitorDNA repairCancer researchPolymeraseDNA Damage RepairMedicineProstateGeneOncologyCancerBiologyInternal medicineGenetics
- Résumé présent dans OpenAlex
- oui