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ePoster Display

590P - PRORADIUM: Prospective analysis of the impact of germline mutations in homologous recombination (HR) genes on the response to radium-223 for metastatic castration resistant prostate cancer (mCRPC)

Date

16 Sep 2021

Session

ePoster Display

Topics

Tumour Site

Prostate Cancer

Presenters

Elena Castro

Citation

Annals of Oncology (2021) 32 (suppl_5): S626-S677. 10.1016/annonc/annonc702

Authors

E. Castro1, R. Lozano Mejorada1, A. Medina2, U. De Giorgi3, N. Romero Laorden4, V. Conteduca3, G. De Velasco5, D. Alameda6, A. Sanz1, J. Puente7, A. Gonzalez del Alba8, P. Borrega9, J.C. Villa Guzmán10, E.M. Fernández-Parra11, A. Rodriguez-Vida12, I. Chirivella13, F. Vazquez14, R. Morales Barrera15, D. Lorente16, D. Olmos1

Author affiliations

  • 1 Prostate Cancer Research Unit, Spanish National Cancer Research Center, 28029 - Madrid/ES
  • 2 Medical Oncology, Centro Oncologico Coruña, A Coruña/ES
  • 3 Department Of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori, Meldola/IT
  • 4 Oncology Dept., Hospital Universitario de La Princesa, 28006 - Madrid/ES
  • 5 Medical Oncology Department, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 6 Genitourinary Oncology Traslational Research Group, Biomedical Research Institute of Málaga (IBIMA), 29010 - Malaga/ES
  • 7 Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, 28040 - Madrid/ES
  • 8 Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid/ES
  • 9 Medical Oncology Department, Hospital San Pedro de Alcántara, Cáceres/ES
  • 10 Medical Oncology Department, Hospital General Universitario de Ciudad Real, Ciudad Real/ES
  • 11 Medical Oncology Department, Hospital Virgen de Valme, Seville/ES
  • 12 Medical Oncology Department, Hospital del Mar, 8003 - Barcelona/ES
  • 13 Department Of Medical Oncology, INCLIVA Biomedical Research Institute, 46010 - Valencia/ES
  • 14 Medical Oncology Department, Hospital General Universitario de Elche, Elche/ES
  • 15 Medical Oncology Dept., Vall d'Hebron University Hospital, 8035 - Barcelona/ES
  • 16 Medical Oncology Department, Consorci Hospitalari Provincial de Castellón, Castellon/ES

Resources

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Abstract 590P

Background

Ra223 is an a-emitter that induces double-strand DNA breaks (DSBs) and selectively targets bone metastases. DSBs is accurately repaired by the HR pathway that is impaired in a significant proportion of mCRPC patients (pts) that harbor pathogenic mutations in HR genes (gHR+). Therefore, we hypothesize that gHR+ may potentiate the effect of Ra223 leading to better efficacy.

Methods

PRORADIUM (NCT02925702) is a prospective observational study of mCRPC pts treated with standard-of-care Ra223. Participants were screened for germline mutation in DDR genes using a multigene panel. Alkaline Phosphatase (ALP) response at 12 weeks was the primary endpoint. PSA response at 12 weeks, time to PSA progression (TTPP), clinical and radiographic progression free survival (cPFS and rPFS) and overall survival (OS) from Ra223 initiation were analysed. Median follow-up from Ra223 was 31 months.

Results

169 mCRPC pts were enrolled in the study. Median age at baseline was 73 years (range 45-90). Performance status ECOG ≤1 was recorded in 85% pts. Median number of prior therapy lines for mCRPC was 2 (range 0-4) including at least one taxane in 63% pts. Most pts (59.2%) received ³5 [LA1] cycles of Ra223. A pathogenic gHR mutation was identified in 15 (8.8%) pts (5 BRCA2, 4 ATM, 1 BRCA1, 1 CHEK2, 1 BRCA1+CHEK2, 1 BRIP1, 1 NBN, 1 BLM). A ³30% decline in ALP at 12 weeks was observed in 71.4% of gHR+ compared to 39.5% of gHR- (p=0.022). No differences in PSA ³50% decline at 12 weeks or TTPP (2.8 vs 3.0 months, p=0.721) were observed. Median rPFS and cPFS were 5.6 vs 6.3 months (p=0.063) and 4.5 vs 6.1 months (p=0.462) in gHR+ and gHR-, respectively. In gATM pts rPFS was 6.1 months and cPFS was 6.6 months. OS from Ra223 was 16.8 in gHR+ and 11.5 in gHR- pts (p=0.078); OS for gATM pts was 28.7 months(p=0.017).

Conclusions

gHR mutations were associated with improved ALP response and a trend towards more prolonged OS suggesting a benefit from Ra223 in some gHR+ patients, particularly those with gATM mutations.

Clinical trial identification

NCT02925702.

Editorial acknowledgement

Legal entity responsible for the study

Instituto de Investigación Biomédica de Málaga (IBIMA).

Funding

Bayer.

Disclosure

E. Castro: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Funding: Pfizer. R. Lozano Mejorada: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Other, Travel/accomodation: Astellas; Financial Interests, Personal, Other, Travel/accomodation: Janssen; Financial Interests, Personal, Other, Travel/accomodation: Sanofi; Financial Interests, Personal, Other, Travel/accomodation: MSD; Financial Interests, Personal, Other, Travel/accomodation: Roche. A. Medina: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Bristol-Meyers-Squibb; Financial Interests, Personal, Invited Speaker: Janssen-Cilag; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol-Meyers-Squibb; Financial Interests, Personal, Advisory Board: Sanofi. U. Giorgi: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol-Meyers-Squibb; Financial Interests, Personal, Advisory Board: Janssen-Cilag; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Other, Travel/accomodation: Bristol-Meyers-Squibb; Financial Interests, Personal, Other, Travel/accomodation: Ipsen; Financial Interests, Personal, Other, Travel/accomodation: Janssen-Cilag; Financial Interests, Personal, Other, Travel/accomodation: Pfizer. N. Romero Laorden: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Travel/accomodation: Janssen-Cilag; Financial Interests, Personal, Other, Travel/accomodation: Pfizer. V. Conteduca: Financial Interests, Personal, Advisory Board: Jansen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Sanofi. G. De Velasco: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen-Cilag; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Bristol-Meyers-Squibb; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Ipsen. J. Puente: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen-Cilag; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Bristol-Meyers-Squibb; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Pierre-Fabre; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Pfizer. A. Gonzalez del Alba: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol-Meyers-Squibb; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Pierre-Fabre; Financial Interests, Personal, Advisory Board: Sanofi. P. Borrega: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Janssen-Cilag; Financial Interests, Personal, Advisory Board: Sanofi. E.M. Fernández-Parra: Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Roche. A. Rodriguez-Vida: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Bristol-Meyers-Squibb; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: Telix; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Merck. I. Chirivella: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol; Financial Interests, Personal, Invited Speaker: Janssen-Cilag; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Travel/accomodation: Astellas; Financial Interests, Personal, Other, Travel/accomodation: Bristol; Financial Interests, Personal, Other, Travel/accomodation: Janssen-Cilag; Financial Interests, Personal, Other, Travel/accomodation: Roche; Financial Interests, Personal, Other, Travel/accomodation: Sanofi. R. Morales Barrera: Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Asofarma; Financial Interests, Personal, Other, Travel/accomodation: Clovis; Financial Interests, Personal, Other, Travel/accomodation: Eli Lilly. D. Lorente: Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Bristol-Meyers-Squibb; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Other, Travel/accomodation: Janssen; Financial Interests, Personal, Other, Travel/accomodation: Astellas. D. Olmos: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: Daiichi-Sankyo; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Other, Personal, Member of the Board of Directors: EORTC. All other authors have declared no conflicts of interest.

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