dc.contributor.author | de Bono, J | |
dc.contributor.author | Mateo, J | |
dc.contributor.author | Fizazi, K | |
dc.contributor.author | Saad, F | |
dc.contributor.author | Shore, N | |
dc.contributor.author | Sandhu, S | |
dc.contributor.author | Chi, KN | |
dc.contributor.author | Sartor, O | |
dc.contributor.author | Agarwal, N | |
dc.contributor.author | Olmos, D | |
dc.contributor.author | Thiery-Vuillemin, A | |
dc.contributor.author | Twardowski, P | |
dc.contributor.author | Mehra, N | |
dc.contributor.author | Goessl, C | |
dc.contributor.author | Kang, J | |
dc.contributor.author | Burgents, J | |
dc.contributor.author | Wu, W | |
dc.contributor.author | Kohlmann, A | |
dc.contributor.author | Adelman, CA | |
dc.contributor.author | Hussain, M | |
dc.date.accessioned | 2020-07-09T11:02:01Z | |
dc.date.issued | 2020-05-28 | |
dc.identifier.citation | The New England journal of medicine, 2020, 382 (22), pp. 2091 - 2102 | |
dc.identifier.issn | 0028-4793 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3836 | |
dc.identifier.eissn | 1533-4406 | |
dc.identifier.doi | 10.1056/nejmoa1911440 | |
dc.description.abstract | 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: 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). All the men had a qualifying alteration in prespecified genes with a direct or indirect role in homologous recombination repair. 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. 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.). | |
dc.format | Print-Electronic | |
dc.format.extent | 2091 - 2102 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | MASSACHUSETTS MEDICAL SOC | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Phenylthiohydantoin | |
dc.subject | Piperazines | |
dc.subject | Phthalazines | |
dc.subject | Androstenes | |
dc.subject | Antineoplastic Agents | |
dc.subject | Genes, BRCA1 | |
dc.subject | Genes, BRCA2 | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Male | |
dc.subject | Ataxia Telangiectasia Mutated Proteins | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.subject | Poly(ADP-ribose) Polymerase Inhibitors | |
dc.subject | Loss of Function Mutation | |
dc.subject | Progression-Free Survival | |
dc.title | Olaparib for Metastatic Castration-Resistant Prostate Cancer. | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1056/nejmoa1911440 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2020-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The New England journal of medicine | |
pubs.issue | 22 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.publication-status | Published | |
pubs.volume | 382 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | De Bono, Johann | |