Serum biomarkers of bone metabolism in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with Radium-223 (Ra223): Resu...

Date 30 September 2019
Event ESMO 2019 Congress
Session Poster Display session 3
Topics Prostate Cancer
Presenter Nuria Romero Laorden
Citation Annals of Oncology (2019) 30 (suppl_5): v325-v355. 10.1093/annonc/mdz248
Authors N. Romero Laorden1, R. Lozano Mejorada2, A. Hernández Jorge3, N. Lainez4, E. Almagro Casado5, O. Fernández Calvo6, S. Hernando7, A. Fernández Freire8, E. Gonzalez Billalabeitia9, I. Chirivella10, R. García Domínguez11, U. Anido Herranz12, F.J. Vazquez Mazon13, S. Ros14, A. Montesa15, G.A. De Velasco Oria de Rueda16, R. Morales Barrera17, D. Lorente18, E. Castro19, D. Olmos Hidalgo20
  • 1Medical Oncology, Hospital Universitario de La Princesa, 28006 - Madrid/ES
  • 2Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid and Instituto de Investigación Biomédica de Málaga (IBIMA), 28029 - Madrid/ES
  • 3Medical Oncology, Onkologikoa, San Sebastian/ES
  • 4Medical Oncology, Complejo Hospitalario de Navarra - Royal Navarre Hospital, 31008 - Pamplona/ES
  • 5Medical Oncology, Hospital Universitario Quirón Salud, Madrid/ES
  • 6Medical Oncology, Complejo Hospitalario de Orense, Ourense/ES
  • 7Medical Oncology, Fundación Hospital Alcorcón, Madrid/ES
  • 8Medical Oncology, Hospital Universitario Torrecárdenass, Almería/ES
  • 9Medical Oncology, Hospital Universitario Morales Meseguer, Murcia/ES
  • 10Medical Oncology, Hospital Clinico Universitario de Valencia, Valencia/ES
  • 11Medical Oncology, Hospital Universitario de Salamanca, Salamanca/ES
  • 12Medical Oncology, Hospital Clínico Universitario de Santiago de Compostela, 15785 - Santiago de Compostela/ES
  • 13Medical Oncology, Hospital General Universitario de Elche, Elche/ES
  • 14Oncology, Hospital Universitario Virgen de la Arrixaca, Murcia/ES
  • 15Medical Oncology, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Málaga/ES
  • 16Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 17Medical Oncology Dept., Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 18Medical Oncology, Hospital Provincial de Castellón, 12002 - Castellón/ES
  • 19Prostate Cancer Clinical Research Unit, Instituto de Investigación Biomédica de Málaga (IBIMA) and Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Malaga/ES
  • 20Prostate Cancer Clinical Research Unit, CNIO- Spanish National Cancer Center, 28029 - Madrid/ES

Abstract

Background

Ra223 is a life-prolonging alpha-emitter bone targeted therapy for mCRPC patients with bone metastases. However, evidence on biomarkers that may help us in patient selection are lacking. Total ALP (tALP) appeared to be a potential marker of Ra223 effect in early studies (Sartor, Ann Oncol, 2017). Other bone-related markers, as bone-specific ALP (BALP), have demonstrated its prognostic value in mCRPC patients with bone metastases (Fizazi K, Eur Urol, 2015; Lara PN, J Natl Cancer Inst, 2014).

Methods

PRORADIUM (NCT022925702) is a prospective multicentre cohort study in mCRPC patients treated with Ra223. The primary aim was to assess the impact of baseline serum biomarkers of bone formation (BALP and C-terminal of type 1 collagen propeptide [CICP]) on overall survival (OS). Secondary aims include the correlation of progression-free survival (PFS), time to PSA progression (TTPP) and skeletal-related events free-survival (SRE-FS) with serum bone markers.

Results

142 out of 168 pts enrolled in the study were included in this preliminary analysis. Median age was 74 yrs, 85.5% pts had ECOG 0-1, 52% pts completed 5-6 cycles of Ra223. Higher baseline levels of BALP and CICP were associated to number of metastases in bone-scan (p = 0.007 and p = 0.016, respectively) and baseline pain (p = 0.014 and p = 0.050, respectively). After a median follow-up of 18 months, 91 deaths were observed, with a median OS of 11.5 months (95%CI: 9.1-13.9). Patients with baseline BALP and CICP values above the median showed a trend to shorter TTPP (BALP: 2.8 vs 3.1 m, p = 0.016; CICP: 2.8 vs 3.0 m, p = 0.091) and PFS (BALP: 4.4 vs 5.1 m, p = 0.070; CICP: 4.2 vs 5.5 m, p = 0.281), respectively. The elevation of bone markers above the median was significantly associated with worse OS (BALP: 8.8 vs 17.9 m, p < 0.001; CICP: 9.4 vs 16.8 m, p = 0.001). There were not associations found with SRE-FS.

Conclusions

Our results suggest that baseline serum markers of bone formation may serve as biomarkers for prognosis in mCRPC patients treated with Ra233.

Clinical trial identification

NCT022925702.

Editorial acknowledgement

Legal entity responsible for the study

IBIMA and CNIO.

Funding

Bayer, CRIS Cancer Foundation, Grant from Instituto de Salud Carlos III (PI16/01565).

Disclosure

N. Romero Laorden: Honoraria (self), Travel / Accommodation / Expenses: Bayer, Astellas Pharma, Janssen-Cilag, Sanofi-Aventis, PharmaMar, MSD, Roche. R. Lozano Mejorada: Honoraria (self): Roche, Janssen-Cilag, Bayer; Research grant / Funding (institution): Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Roche, Janssen-Cilag, Astellas Pharma. E. Almagro Casado: Honoraria (self): MSD; Travel / Accommodation / Expenses: BMS. E. Gonzalez Billalabeitia: Travel / Accommodation / Expenses: BMS, Pfizer, Janssen-Cilag, Astellas Pharma, Sanofi. A. Montesa: Advisory / Consultancy: Janssen-Cilag, Pfizer, Sanofi, Astellas Pharma; Travel / Accommodation / Expenses: Pfizer. G.A. De Velasco Oria de Rueda: Honoraria (self), Advisory / Consultancy: Pfizer, Novartis, Ipsen, Astellas Pharma, BMS, Bayer, MSD, Roche. R. Morales Barrera: Honoraria (self): MSD, Sanofi, AstraZeneca, Janssen, Roche/Genentech; Advisory / Consultancy: MSD, Sanofi, AstraZeneca, Janssen, Roche/Genentech; Speaker Bureau / Expert testimony: MSD, Sanofi, AstraZeneca, Asofarma, Janssen; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, INC, Astellas Pharma, AstraZeneca, Aveo Pharmaceuticals, Bayer, Blueprint Medicines Corporation, BN Immunotherapeutics, Boehringer Ingelheim España, BMS, Clovis Oncology, Cougar Technology, Deciphera Pharmaceuticals LL; Travel / Accommodation / Expenses: MSD, Roche, Lilly, Clovis Oncology, Bayer, Janssen-Cilag, Astellas Pharma, AstraZeneca. D. Lorente: Honoraria (self): Janssen-Cilag, Bayer, Astellas Pharma, Sanofi; Advisory / Consultancy: Janssen-Cilag, Bayer, Sanofi; Travel / Accommodation / Expenses: Sanofi, Astellas, Janssen-Cilag, Celgene. E. Castro: Honoraria (self): Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer; Advisory / Consultancy: Bayer, Janssen-Cilag; Research grant / Funding (institution): Janssen-Cilag, AstraZeneca, Bayer, Genentech, Roche, Pfizer, Astellas Medivation, Tokai Pharmaceuticals; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, Astellas Pharma. D. Olmos Hidalgo: Honoraria (self): Janssen-Cilag, Bayer, Sanofi; Advisory / Consultancy: Bayer, Janssen-Cilag, AstraZeneca, Clovis Oncology; Research grant / Funding (institution): Bayer, Janssen, AstraZeneca, Roche/Genentech, Medivation/Pfizer, Astellas, Tokai, MSD, GSK; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Ipsen. All other authors have declared no conflicts of interest.