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Genitourinary tumours, prostate

4599 - PROREPAIR-B: A prospective cohort study of DNA repair defects in metastatic castration resistant prostate cancer (mCRPC)

Date

08 Sep 2017

Session

Genitourinary tumours, prostate

Presenters

Elena Castro Marcos

Citation

Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440

Authors

E. Castro Marcos1, N. Romero Laorden1, J.M. Piulats Rodriguez2, A. del Pozo3, M.I. Sáez4, A. Medina Colmenero5, J. Puente6, J.C. Silla-Castro3, R. Lozano Mejorada1, I. Garcia-Carbonero7, L. Rivera1, M.J. Mendez Vidal8, R. Morales Barrera9, E.M. Fernandez Parra10, Y. Cendón Flórez1, P. Borrega11, M.A. Gonzalez Del Alba Baamonde12, C. Pritchard13, P. Lapunzina14, D. Olmos Hidalgo1

Author affiliations

  • 1 Prostate Cancer Unit, CNIO- Spanish National Cancer Center, 28029 - Madrid/ES
  • 2 Medical Oncology, Insitut Catalán d'Oncología, 8907 - Barcelona/ES
  • 3 Instituto De Genética Médica Y Molecular, Hospital Universitario La paz, Madrid/ES
  • 4 Medical Oncology, H Universitario Virgen de la Victoria y Regional de Málaga, Malaga/ES
  • 5 Oncología Médica, Centro Oncologico de A Coruña, A Coruña/ES
  • 6 Medical Oncology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 7 Medical Oncology, Hospital Universitario Virgen de la Salud, Toledo/ES
  • 8 Medical Oncology, University Hospital Reina Sofia, 14004 - Cordoba/ES
  • 9 Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 10 Medical Oncology, Hospital Nuestra Señora de Valme, 41014 - Sevilla/ES
  • 11 Medical Oncology, H. San pedro de Alcántara, 10003 - Cáceres/ES
  • 12 Medical Oncology, Hospital Universitario Son Espases, 7010 - Palma de Mallorca/ES
  • 13 Laboratory Medicine, University of Washington, Washington/US
  • 14 Medical Genetics And Molecular Institute (ingemm), Instituto de Investigación Hospital Universitario La Paz, 28046 - Madrid/ES
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Abstract 4599

Background

Germline mutations in DNA repair genes have been associated with poor prostate cancer outcomes and progression to metastatic disease, but no conclusive data are available regarding survival from mCRPC and response to currently approved survival-prolonging therapies (SPT).

Methods

Prospective multicentre observational study of newly diagnosed mCRPC patients with unknown germline mutation status at study entry. Patients were treated at physician-choice’s with either abiraterone, enzalutamide, docetaxel, cabazitaxel or Ra-223. Primary endpoint was to assess the impact or BRCA1, BRCA2, ATM and PALB2 germline mutations on cause-specific survival (CSS) from diagnosis of mCRPC. It required enrolling at least 408 patients and to observe at least 171 deaths to demonstrate a CSS HR of germline mutation carriers (C) vs non-carriers (NC) equal to 3 (α = 0.05 & β = 0.20). Secondary endpoints included the association of those mutations to the response to SPT.

Results

From January 2013 to April 2016, 419 eligible patients from 38 Spanish institutions were enrolled. Identified C were 14 BRCA2, 8 ATM and 4 BRCA1 (6.2%). A non-significant (NS) trend to younger age (median 66.5 vs 71.6 yrs, p = 0.16) was observed in C compared to NC. Median time from ADT initiation to mCRPC in C and NC was 23.7 vs 26.7 m (p = 0.22); in the BRCA2 subgroup was 18 m (p = 0.24). Other baseline characteristics were also NS different between C and NC at 1st SPT initiation: ECOG 0-1 (92% vs 88%), median PSA (27.9 vs 31.0), bone (96% vs 86%), nodal (48% vs 52%) and visceral (12% vs 16%) metastasis. 1st SPT in C and NC were a taxane for 63% and 46% for novel AR targeting therapies (ART) for 37% and 53%, respectively. After a median follow-up of 36 m, 207 prostate-cancer deaths were observed. Median CSS from mCRPC was 28.5 m in C vs 36.0 m in NC (p = 0.5), and 17.4 m in the BRCA2 subgroup (p = 0.02). Median CSS and PFS from 1st taxane in C and NC were 17.3 vs 24.5 m, p = 0.6 (BRCA2 12.8 m, p 

Conclusions

When all C considered, non-significant trends to worse CSS from mCRPC, from 1st taxane and from 1st ART were observed. Nonetheless, pre-planned subgroup analyses suggest that BRCA2 mutations are associated with significantly worse outcomes.

Clinical trial identification

NCT03075735

Legal entity responsible for the study

Spanish National Cancer Research Centre (CNIO) and Instituto de Investigación Biomédica de Málaga (IBIMA)

Funding

Prostate Cancer Foundation, Fundación CRIS Contra el Cáncer, Fundación Obra Social La Caixa, Instituto de Salud Carlos III

Disclosure

All authors have declared no conflicts of interest.

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