dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Schmid, Sabine |
dc.contributor.author | Omlin, Aurelius |
dc.contributor.author | Higano, Celestia |
dc.contributor.author | Sweeney, Christopher |
dc.contributor.author | Martinez Chanza, Nieves |
dc.contributor.author | Mehra, Niven |
dc.contributor.author | Morales Barrera, Rafael |
dc.date.accessioned | 2021-09-21T10:53:48Z |
dc.date.available | 2021-09-21T10:53:48Z |
dc.date.issued | 2020-10-28 |
dc.identifier.citation | Schmid 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.issn | 2574-3805 |
dc.identifier.uri | https://hdl.handle.net/11351/6340 |
dc.description | Chemotherapy; Advanced Prostate Cancer; DNA Repair |
dc.description.abstract | Importance 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.iso | eng |
dc.publisher | American Medical Association |
dc.relation.ispartofseries | Jama Network Open;3(10) |
dc.rights | Attribution 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.source | Scientia |
dc.subject | Pròstata - Càncer - Quimioteràpia |
dc.subject | ADN - Reparació |
dc.subject.mesh | Prostatic Neoplasms |
dc.subject.mesh | /drug therapy |
dc.subject.mesh | DNA Repair-Deficiency Disorders |
dc.title | Activity of Platinum-Based Chemotherapy in Patients With Advanced Prostate Cancer With and Without DNA Repair Gene Aberrations |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1001/jamanetworkopen.2020.21692 |
dc.subject.decs | neoplasias de la próstata |
dc.subject.decs | /farmacoterapia |
dc.subject.decs | trastornos por deficiencias en la reparación del ADN |
dc.relation.publishversion | https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2772301 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut 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.pmid | 33112397 |
dc.identifier.wos | 000588112500001 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |