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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorSchmid, Sabine
dc.contributor.authorOmlin, Aurelius
dc.contributor.authorHigano, Celestia
dc.contributor.authorSweeney, Christopher
dc.contributor.authorMartinez Chanza, Nieves
dc.contributor.authorMehra, Niven
dc.contributor.authorMorales Barrera, Rafael
dc.date.accessioned2021-09-21T10:53:48Z
dc.date.available2021-09-21T10:53:48Z
dc.date.issued2020-10-28
dc.identifier.citationSchmid S, Omlin A, Higano C, Sweeney C, Martinez Chanza N, Mehra N, et al. Activity of Platinum-Based Chemotherapy in Patients With Advanced Prostate Cancer With and Without DNA Repair Gene Aberrations. JAMA Netw Open. 2020 Oct 28;3(10):e2021692.
dc.identifier.issn2574-3805
dc.identifier.urihttp://hdl.handle.net/11351/6340
dc.descriptionChemotherapy; Advanced Prostate Cancer; DNA Repair
dc.description.abstractImportance DNA repair gene aberrations occur in 20% to 30% of patients with castration-resistant prostate cancer (CRPC), and some of these aberrations have been associated with sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition or platinum-based treatments. However, previous trials assessing platinum-based treatments in patients with CRPC have mostly included a biomarker-unselected population; therefore, efficacy in these patients is unknown. Objective To characterize the antitumor activity of platinum-based therapies in men with CRPC with or without DNA repair gene alterations. Design, Setting, and Participants In this case series, data from 508 patients with CRPC treated with platinum-based therapy were collected from 25 academic centers from 12 countries worldwide. Patients were grouped by status of DNA repair gene aberrations (ie, cohort 1, present; cohort 2, not detected; and cohort 3, not tested). Data were collected from January 1986 to December 2018. Data analysis was performed in 2019, with data closure in April 2019. Exposure Treatment with platinum-based compounds either as monotherapy or combination therapy. Main Outcomes and Measures The primary end points were as follows: (1) antitumor activity of platinum-based therapy, defined as a decrease in prostate-specific antigen (PSA) level of at least 50% and/or radiological soft tissue response in patients with measurable disease and (2) the association of response with the presence or absence of DNA repair gene aberrations. Results A total of 508 men with a median (range) age of 61 (27-88) years were included in this analysis. DNA repair gene aberrations were present in 80 patients (14.7%; cohort 1), absent in 98 (19.3%; cohort 2), and not tested in 330 (65.0%; cohort 3). Of 408 patients who received platinum-based combination therapy, 338 patients (82.8%) received docetaxel, paclitaxel, or etoposide, and 70 (17.2%) received platinum-based combination treatment with another partner. A PSA level decrease of at least 50% was seen in 33 patients (47.1%) in cohort 1 and 26 (36.1%) in cohort 2 (P = .20). In evaluable patients, soft tissue responses were documented in 28 of 58 patients (48.3%) in cohort 1 and 21 of 67 (31.3%) in cohort 2 (P = .07). In the subgroup of 44 patients with BRCA2 gene alterations, PSA level decreases of at least 50% were documented in 23 patients (63.9%) and soft tissue responses in 17 of 34 patients (50.0%) with evaluable disease. In cohort 3, PSA level decreases of at least 50% and soft tissue responses were documented in 81 of 284 patients (28.5%) and 38 of 185 patients (20.5%) with evaluable disease, respectively. Conclusions and Relevance In this study, platinum-based treatment was associated with relevant antitumor activity in a biomarker-positive population of patients with advanced prostate cancer with DNA repair gene aberrations. The findings of this study suggest that platinum-based treatment may be considered an option for these patients.
dc.language.isoeng
dc.publisherAmerican Medical Association
dc.relation.ispartofseriesJama Network Open;3(10)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectPròstata - Càncer - Quimioteràpia
dc.subjectADN - Reparació
dc.subject.meshProstatic Neoplasms
dc.subject.mesh/drug therapy
dc.subject.meshDNA Repair-Deficiency Disorders
dc.titleActivity of Platinum-Based Chemotherapy in Patients With Advanced Prostate Cancer With and Without DNA Repair Gene Aberrations
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1001/jamanetworkopen.2020.21692
dc.subject.decsneoplasias de la próstata
dc.subject.decs/farmacoterapia
dc.subject.decstrastornos por deficiencias en la reparación del ADN
dc.relation.publishversionhttps://jamanetwork.com/journals/jamanetworkopen/fullarticle/2772301
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Schmid S] Department of Medical Oncology and Haematology, Cantonal Hospital of St Gallen, St Gallen, Switzerland. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada. [Omlin A] Department of Medical Oncology and Haematology, Cantonal Hospital of St Gallen, St Gallen, Switzerland. [Higano C] Seattle Cancer Care Alliance, University of Washington, Seattle. [Sweeney C, Martinez Chanza N] Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts. [Mehra N] Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands. [Morales-Barrera R] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid33112397
dc.identifier.wos000588112500001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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