dc.contributor.author | Mateo, J | |
dc.contributor.author | Cheng, HH | |
dc.contributor.author | Beltran, H | |
dc.contributor.author | Dolling, D | |
dc.contributor.author | Xu, W | |
dc.contributor.author | Pritchard, CC | |
dc.contributor.author | Mossop, H | |
dc.contributor.author | Rescigno, P | |
dc.contributor.author | Perez-Lopez, R | |
dc.contributor.author | Sailer, V | |
dc.contributor.author | Kolinsky, M | |
dc.contributor.author | Balasopoulou, A | |
dc.contributor.author | Bertan, C | |
dc.contributor.author | Nanus, DM | |
dc.contributor.author | Tagawa, ST | |
dc.contributor.author | Thorne, H | |
dc.contributor.author | Montgomery, B | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | Sandhu, S | |
dc.contributor.author | Rubin, MA | |
dc.contributor.author | Nelson, PS | |
dc.contributor.author | de Bono, JS | |
dc.date.accessioned | 2018-03-01T14:13:09Z | |
dc.date.issued | 2018-05-01 | |
dc.identifier.citation | European urology, 2018, 73 (5), pp. 687 - 693 | |
dc.identifier.issn | 0302-2838 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1468 | |
dc.identifier.eissn | 1873-7560 | |
dc.identifier.doi | 10.1016/j.eururo.2018.01.010 | |
dc.description.abstract | BACKGROUND: Germline DNA damage repair gene mutation (gDDRm) is found in >10% of metastatic prostate cancer (mPC). Their prognostic and predictive impact relating to standard therapies is unclear. OBJECTIVE: To determine whether gDDRm status impacts benefit from established therapies in mPC. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective, international, observational study. Medical records were reviewed for 390 mPC patients with known gDDRm status. All 372 patients from Royal Marsden (UK), Weill-Cornell (NY), and University of Washington (WA) were previously included in a prevalence study (Pritchard, NEJM 2016); the remaining 18 were gBRCA1/2m carriers, from the kConFab consortium, Australia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Response rate (RR), progression-free survival (PFS), and overall survival (OS) data were collected. To account for potential differences between cohorts, a mixed-effect model (Weibull distribution) with random intercept per cohort was used. RESULTS AND LIMITATIONS: The gDDRm status was known for all 390 patients (60 carriers of gDDRm [gDDRm+], including 37 gBRCA2m, and 330 cases not found to carry gDDRm [gDDRm-]); 74% and 69% were treated with docetaxel and abiraterone/enzalutamide, respectively, and 36% received PARP inhibitors (PARPi) and/or platinum. Median OS from castration resistance was similar among groups (3.2 vs 3.0 yr, p=0.73). Median docetaxel PFS for gDDRm+ (6.8 mo) was not significantly different from that for gDDRm- (5.1 mo), and RRs were similar (gDDRm+=61%; gDDRm-=54%). There were no significant differences in median PFS and RR on first-line abiraterone/enzalutamide (gDDRm+=8.3 mo, gDDRm-=8.3 mo; gDDRm+=46%, gDDRm-=56%). Interaction test for PARPi/platinum and gDDRm+ resulted in an OS adjusted hazard ratio of 0.59 (95% confidence interval 0.28-1.25; p=0.17). Results are limited by the retrospective nature of the analysis. CONCLUSIONS: mPC patients with gDDRm appeared to benefit from standard therapies similarly to the overall population; prospective studies are ongoing to investigate the impact of PARPi/platinum. PATIENT SUMMARY: Patients with inherited DNA repair mutations benefit from standard therapies similarly to other metastatic prostate cancer patients. | |
dc.format | Print-Electronic | |
dc.format.extent | 687 - 693 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCIENCE BV | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Androgen Antagonists | |
dc.subject | Antineoplastic Agents | |
dc.subject | Biopsy, Needle | |
dc.subject | Prognosis | |
dc.subject | Disease-Free Survival | |
dc.subject | Treatment Outcome | |
dc.subject | Immunohistochemistry | |
dc.subject | Proportional Hazards Models | |
dc.subject | Risk Assessment | |
dc.subject | Survival Analysis | |
dc.subject | Retrospective Studies | |
dc.subject | Cohort Studies | |
dc.subject | DNA Repair | |
dc.subject | Germ-Line Mutation | |
dc.subject | Internationality | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Male | |
dc.subject | Kaplan-Meier Estimate | |
dc.subject | Neoplasm Grading | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.title | Clinical Outcome of Prostate Cancer Patients with Germline DNA Repair Mutations: Retrospective Analysis from an International Study. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-01-09 | |
rioxxterms.versionofrecord | 10.1016/j.eururo.2018.01.010 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2018-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | European urology | |
pubs.issue | 5 | |
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/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers | |
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/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.publication-status | Published | |
pubs.volume | 73 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | Rescigno, Pasquale | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | De Bono, Johann | |