دورية أكاديمية
PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer
| العنوان: | PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer |
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| المؤلفون: | Castro, Elena, Romero-Laorden, Nuria, Pozo, Ángela del, Lozano, Rebeca, Medina, Ana, Puente, Javier, Piulats, Josep Maria, Lorente, David, Sáez, María Isabel, Morales-Barrera, Rafael, González-Billalabeitia, E., Cendón, Ylenia, García-Carbonero, Iciar, Borrega, Pablo, Méndez-Vidal, M. J., Montesa, Álvaro, Nombela, Paz, Fernández-Parra, Eva, González del Alba, Aránzazu, Villa-Guzmán, José Carlos, Ibáñez, Kristina, Rodríguez-Vida, Alejo, Magraner-Pardo, Lorena, Perez-Valderrama, Begoña, Vallespin, Elena, Gallardo, Enrique, Vázquez, Sergio, Pritchard, Colin C., Lapunzina, Pablo, Olmos, David |
| المساهمون: | Fundación CRIS contra el Cáncer, Prostate Cancer Foundation, Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Fundación Científica Asociación Española Contra el Cáncer, Ministerio de Educación, Cultura y Deporte (España) |
| بيانات النشر: | American Society of Clinical Oncology |
| سنة النشر: | 2019 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | [Purpose] Germline mutations in DNA damage repair (DDR) genes are identified in a significant proportion of patients with metastatic prostate cancer, but the clinical implications of these genes remain unclear. This prospective multicenter cohort study evaluated the prevalence and effect of germline DDR (gDDR) mutations on metastatic castration-resistance prostate cancer (mCRPC) outcomes. ; [Patients and Methods] Unselected patients were enrolled at diagnosis of mCRPC and were screened for gDDR mutations in 107 genes. The primary aim was to assess the impact of ATM/BRCA1/BRCA2/PALB2 germline mutations on cause-specific survival (CSS) from diagnosis of mCRPC. Secondary aims included the association of gDDR subgroups with response outcomes for mCRPC treatments. Combined progression-free survival from the first systemic therapy (PFS) until progression on the second systemic therapy (PFS2) was also explored. ; [Results] We identified 68 carriers (16.2%) of 419 eligible patients, including 14 with BRCA2, eight with ATM, four with BRCA1, and none with PALB2 mutations. The study did not reach its primary end point, because the difference in CSS between ATM/BRCA1/BRCA2/PALB2 carriers and noncarriers was not statistically significant (23.3 v 33.2 months; P = .264). CSS was halved in germline BRCA2 (gBRCA2) carriers (17.4 v 33.2 months; P = .027), and gBRCA2 mutations were identified as an independent prognostic factor for CCS (hazard ratio [HR], 2.11; P = .033). Significant interactions between gBRCA2 status and treatment type (androgen signaling inhibitor v taxane therapy) were observed (CSS adjusted P = .014; PFS2 adjusted P = .005). CSS (24.0 v 17.0 months) and PFS2 (18.9 v 8.6 months) were greater in gBRCA2 carriers treated in first line with abiraterone or enzalutamide compared with taxanes. Clinical outcomes did not differ by treatment type in noncarriers. ; [Conclusion] gBRCA2 mutations have a deleterious impact on mCRPC outcomes that may be affected by the first line of treatment used. Determination of gBRCA2 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0732-183X 1527-7755 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/IJCI-2014-19129; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/RYC-2015-18625; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SVP-2013-067937; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SVP-2014-068895; https://doi.org/10.1200/JCO.18.00358Test; Sí; Journal of Clinical Oncology 37(69: 490-503 (2019); http://hdl.handle.net/10261/213298Test; http://dx.doi.org/10.13039/100000892Test; http://dx.doi.org/10.13039/501100004587Test; http://dx.doi.org/10.13039/501100010198Test; http://dx.doi.org/10.13039/501100002704Test; http://dx.doi.org/10.13039/501100003176Test |
| DOI: | 10.1200/JCO.18.00358 |
| DOI: | 10.13039/100000892 |
| DOI: | 10.13039/501100004587 |
| DOI: | 10.13039/501100010198 |
| DOI: | 10.13039/501100002704 |
| DOI: | 10.13039/501100003176 |
| الإتاحة: | https://doi.org/10.1200/JCO.18.00358Test https://doi.org/10.13039/100000892Test https://doi.org/10.13039/501100004587Test https://doi.org/10.13039/501100010198Test https://doi.org/10.13039/501100002704Test https://doi.org/10.13039/501100003176Test http://hdl.handle.net/10261/213298Test |
| حقوق: | none |
| رقم الانضمام: | edsbas.6DF87C9E |
| قاعدة البيانات: | BASE |
| تدمد: | 0732183X 15277755 |
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| DOI: | 10.1200/JCO.18.00358 |