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Poster Display session 3

4349 - Impact of treatment sequence in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): data from the prospective PROREPAIR-B study.


30 Sep 2019


Poster Display session 3


Tumour Site

Prostate Cancer


Carlo Cattrini


Annals of Oncology (2019) 30 (suppl_5): v325-v355. 10.1093/annonc/mdz248


C. Cattrini1, N. Romero Laorden2, E. Castro3, I. García-Carbonero4, J.M. Piulats5, J. Puente6, B. P. Valderrama7, J.C. Villa Guzman8, E. Gonzalez Billalabeitia9, R. Morales Barrera10, R. Lozano Mejorada11, R. Luque12, E. Martinez Ortega13, J.A. Arranz Arija14, E. Gallardo Diaz15, A. Pinto Marin16, E. Almagro Casado17, M.J. Mendez Vidal18, D. Olmos Hidalgo19, D. Lorente20

Author affiliations

  • 1 Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO) and University of Genoa, 28029 - Madrid/ES
  • 2 Medical Oncology, Hospital Universitario de La Princesa, 28006 - Madrid/ES
  • 3 Prostate Cancer Clinical Research Unit, Instituto de Investigación Biomédica de Málaga (IBIMA) and Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Malaga/ES
  • 4 Medical Oncology, Hospital Virgen de la Salud de Toledo, Toledo/ES
  • 5 Department Of Medical Oncology, Genitourinary, Melanoma And Sarcoma Unit, Institut Català d’Oncologia-IDIBELL-CIBERONC, Barcelona/ES
  • 6 Medical Oncology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 7 Medical Oncology, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 8 Medical Oncology, Hospital General Ciudad Real, 13005 - Ciudad Real/ES
  • 9 Medical Oncology, Hospital Universitario Morales Meseguer, Murcia/ES
  • 10 Medical Oncology Dept., Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 11 Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), 28029 - Madrid/ES
  • 12 Service Of Medical Oncology, Hospital Universitario Virgen de las Nieves, 18014 - Granada/ES
  • 13 Medical Oncology, Complejo Hospitalario de Jaen Universidad de Jaen, 23007 - Jaen/ES
  • 14 Medical Oncology, Hospital General Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 15 Dept. Oncology, Hospital de Sabadell Corporacis Parc Tauli, 08208 - Sabadell/ES
  • 16 Medical Oncology, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 17 Medical Oncology, Hospital Universitario Quirón Salud, Madrid/ES
  • 18 Medical Oncology, Reina Sofía University Hospital, Cordoba/ES
  • 19 Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid and Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, 28029 - Madrid/ES
  • 20 Medical Oncology, Hospital Provincial de Castellón, 12002 - Castellón/ES


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Abstract 4349


Abiraterone (Abi), enzalutamide (Enz) and docetaxel (Doc) are all approved first-line (1L) treatment options for mCRPC. However, the optimal treatment sequence has not been established yet. In the present analysis, we explored the outcomes of pts treated with 1L Doc or Abi/Enz in the prospective PROREPAIR-B cohort study (NCT03075735).


We assessed the impact of 1L treatment options (Doc vs Abi/Enz) on progression-free survival to 1L therapy (PFS) and overall survival (OS). Uni- (UV) and multivariable (MV) Cox-regression models were used. MV model covariates included age (≥75 years), local therapy, Gleason Score, visceral metastases, metastases at diagnosis, phosphatase alkaline (ALP) (≥ULN), lactate dehydrogenase (LDH) (≥ULN), haemoglobin (Hb) (≤LNL), albumin (≤LNL) and ECOG performance status.


Of 419 pts enrolled in the study, 406 received 1L Doc (n = 188) or Abi/Enz (n = 218). Overall, pts receiving Doc were younger (p = 0.002), had higher rates of visceral metastases (17.6% vs 8.7%, p = 0.008), ALP (52.1% vs 40.4%, p = 0.018), LDH (48.1% vs 31.2%, p < 0.001), lower Hb (7.4% vs 2.8%, p = 0.029) and albumin (11.3% vs 4.6%). The median follow-up was 40 months. PFS was longer in pts receiving 1L Abi/Enz vs Doc (10.8 vs 8.3 months, HR: 0.5, p < 0.001). 123/188 pts treated with 1L-Doc received second-line (2L) Abi/Enz: 30 received other 2L and 35 had not started 2L. 111/216 pts treated with 1L-Abi/Enz received 2L Doc, 26 were started on other 2L and 79 had not initiated 2L. Choice of first-line agent was not associated with OS in the MV model. Similar results were found in the elderly population. Of 137 aged ≥ 75 years, 48 received Doc and 88 Abi/Enza as first-line therapy. PFS favoured 1L Abi/Enz vs Doc (9.6 vs 8.3m, HR: 0.52, p = 0.001), whereas no difference was found in terms of OS (28.2 vs 24.8m, respectively, HR: 1.18, p = 0.474).


Pts treated with 1L Doc had worse baseline prognostic features. Despite a longer PFS was observed in pts treated with 1L Abi/Enz vs Doc, no difference in OS was found between the treatment sequences. Similar results were observed in the elderly population. Biomarker-driven pts selection is needed to identify the optimal sequence.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

Centro Nacional de Investigaciones Oncológicas (CNIO).


Unrestricted grant from Fundación Cris Contra el Cancer; three investigator awards from the Prostate Cancer Foundation (C.C.P. [2013], D.O. [2014], and E.C. [2017]); and three grants from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (No. PI13/01287 and PI16/01565 to D.O. and No. PI15/01471 to P.L.). During the conduct of this study, E.C., D.O., P.N., and L.M-P. were supported by grants from Ministerio de Economía, Industria y Competitividad (No. JCI-2014-19129 [E.C.], No. RYC-2015-18625 [D.O.], No. SVP-2013-067937 [P.N.], No. SVP-2014-068895 [L.M.]); D.O. was also funded by a Return fellowship from Fundación Científica de la Asociación Española Contra el Cancer, 2012-2015; N.R.L. and R.L., by grants from Instituto de Salud Carlos III (No. CM14-00200 to N.R.L. and No. CM17-00221 [R.L.]); and Y.C., by a grant from Ministerio de Educación, Cultura y Deportes (No. FPU15/05126). C.C.P. was supported by a congressional-designated medical research program award (No. CMRP-PC131820).


C. Cattrini: Travel / Accommodation / Expenses: Novartis, Ipsen. N. Romero Laorden: Honoraria (self): MSD, Sanofi-Aventis, Astellas, Janssen-Cilag; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, PharmaMar; Research grant / Funding (institution): Bayer, Astellas, Janssen, Sanofi. E. Castro: Honoraria (self): Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer; Advisory / Consultancy: Bayer, Janssen-Cilag; Research grant / Funding (institution): Janssen-Cilag, AstraZeneca, Bayer; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, Astellas Pharma. I. García-Carbonero: Advisory / Consultancy: Janssen Oncology, Astellas Pharma, Bayer, Sanofi; Travel / Accommodation / Expenses: Astellas Pharma, Janssen, Sanofi, Bayer. J.M. Piulats: Advisory / Consultancy: Janssen Oncology, Astellas Pharma, VCN Biosciences, Clovis Oncology, Roche, Genentech, Bristol-Myers Squibb, Merck Sharp & Dohme; Research grant / Funding (institution): Bristol-Myers Squibb, AstraZeneca, MedImmune, Merck Sharp & Dohme, Pfizer, EMD Serono, Incyte, Janssen Oncology; Travel / Accommodation / Expenses: Janssen Oncology, Roche, Bristol-Myers Squibb. J. Puente: Advisory / Consultancy: Pfizer, Astellas Pharma, Janssen-Cilag, Merck Sharp & Dohme, Bayer, Roche, Bristol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Ipsen, Eisai, EUSA Pharma, Sanofi; Speaker Bureau / Expert testimony: Pierre Fabre, Celgene, Kiowa, Novartis, Lilly; Research grant / Funding (institution): Astellas Pharma, Pfizer; Research grant / Funding (institution): Pfizer, Roche, Janssen-Cilag. B. P. Valderrama: Honoraria (self): Pierre Fabre, Astellas Pharma, Novartis, Bristol-Myers Squibb, Ipsen; Advisory / Consultancy: Astellas Pharma, Novartis, Pfizer, Pierre Fabre, Bayer, Sanofi, Bristol-Myers Squibb, Roche, Ipsen; Travel / Accommodation / Expenses: Janssen-Cilag, Bristol-Myers Squibb. E. Gonzalez Billalabeitia: Travel / Accommodation / Expenses: Bristol-Myers Squibb, Pfizer, Janssen-Cilag, Astellas Pharma, Sanofi. R. Morales Barrera: Honoraria (self): MSD, Sanofi, AstraZeneca, Asofarma, Johnson and Johnson, Roche/Genentech; Advisory / Consultancy: MSD, Sanofi, AstraZeneca, Asofarma, Johnson and Johnson, Roche/Genentech; Speaker Bureau / Expert testimony: MSD. Sanofi, AstraZeneca, Asofarma, Johnson and Johnson; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma., AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim España, S.A., Bristol-Myers Squibb Intern; Travel / Accommodation / Expenses: MSD, Roche/Genentech, Lilly, Clovis Oncology, Bayer, Johnson and Johnson, Astellas Pharma, AstraZeneca. R. Lozano Mejorada: Honoraria (self): Roche, Janssen-Cilag, Bayer; Research grant / Funding (institution): Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Roche, Janssen-Cilag, Astellas Pharma. R. Luque: Honoraria (self), Travel / Accommodation / Expenses: Janssen-Cilag, Sanofi Aventis, Astellas Medivation, Roche, Novartis, Pfizer, Bristol-Myers Squibb, EUSA Pharma. E. Martinez Ortega: Honoraria (self), Travel / Accommodation / Expenses: Sanofi Aventis, Roche, Pfizer Bristol Mayers Squibb, EUSA Pharma and IPSEN. J.A. Arranz Arija: Honoraria (self): Novartis MSD Oncology Janssen-Cilag EUSA Pharma Astellas Pharma Bristol-Myers Squibb; Advisory / Consultancy: Pfizer Astellas Pharma Janssen-Cilag Novartis Bayer Ipsen MSD Oncology Bristol-Myers Squibb EUSA Pharma; Research grant / Funding (institution): Novartis Pierre Fabre Bristol-Myers Squibb; Travel / Accommodation / Expenses: Bristol-Myers Squibb Janssen-Cilag MSD Oncology Pfizer. E. Gallardo Diaz: Honoraria (self): Astellas Pharma, Roche, Bristol-Myers Squibb, Novartis; Advisory / Consultancy: Pfizer, Bayer Schering Pharma, Janssen Oncology, Astellas Pharma, Roche, Bristol-Myers Squibb, Sanofi, Ipsen, Eisai, Rovi, Daiichi Sankyo, EUSA Pharma; Speaker Bureau / Expert testimony: Rovi, LEO Pharma, Menarini, Bristol-Myers Squibb, Ipsen, Astellas Pharma, Roche, Daiichi Sankyo; Travel / Accommodation / Expenses: Pfizer, Astellas Pharma, Pierre Fabre, Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Janssen, Roche. E. Almagro Casado: Speaker Bureau / Expert testimony: MSD; Travel / Accommodation / Expenses: Bristol-Myers Squibb. M.J. Mendez Vidal: Advisory / Consultancy: Janssen-Cilag, Pfizer, Astellas Pharma, Sanofi, Bayer, Bristol-Myers Squibb, Novartis, Roche; Travel / Accommodation / Expenses: Janssen-Cilag, Pfizer, Astellas Pharma, Bristol-Myers Squibb. D. Olmos Hidalgo: Speaker Bureau / Expert testimony: Astellas, Bayer, Janssen, Sanofi; Advisory / Consultancy: Astellas, AstraZeneca, Bayer, Genentech, Janssen, Clovis; Research grant / Funding (institution): Astellas, AstraZeneca, Bayer, Genentech/Roche, Janssen (Incl.Aragon), Medivation/Pfizer, Tokai, MSD, GSK; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Ipsen. D. Lorente: Honoraria (self): Janssen-Cilag, Bayer, Astellas Pharma, Sanofi; Advisory / Consultancy: Janssen-Cilag, Bayer, Sanofi; Travel / Accommodation / Expenses: Sanofi, Astellas, Janssen-Cilag, Celgene. All other authors have declared no conflicts of interest.

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