Abstract 606P
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 radium-223. 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
169 pts were included, serum biomarkers were successfully analysed in 153 pts. Median age was 74.4 yrs, 85.2% pts had ECOG 0-1, 57.5% patients completed 5-6 cycles of Ra223. tALP was strongly correlated with shorter rPFS and OS (P<0.001). Higher baseline levels of BALP and CICP were associated to number of metastases in bone-scan (p=0.002 and p=0.001, respectively) and baseline pain (p=0.003, p=0.028, respectively). After a median follow-up of 31.1 months, 147 deaths were observed, with a median OS of 12.1 months (95%CI: 9.5-14.7). Continuous value of BALP and CICP correlated with a shorter TTPP (BALP: Q1 5.4m/Q4 3.3m, p=0.013; CICP: Q1 5.5m/Q4 3.6m, p=0.011) and rPFS (BALP: Q1 10.2m/Q4 5.4m, p=0.009; CICP: Q1 9.3m/Q4 6.9m, p=0.037), respectively. The elevation of 3-4 bone biomarkers over the median was significantly associated with worse OS (15.2 vs 9.9 m, HR 1.63, p=0.007, Fig 1). There were not associations found with SRE-FS.
Conclusions
Our results suggest that baseline serum markers of bone formation can serve as biomarkers for prognosis in mCRPC patients treated with Ra223.
Clinical trial identification
NCT022925702.
Editorial acknowledgement
Legal entity responsible for the study
CNIO - Spanish National Cancer Research Centre.
Funding
Bayer + academic grants.
Disclosure
N. Romero Laorden: Financial Interests, Personal and Institutional, Research Grant: Janssen; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Advisory Role: MSD; Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: Astellas; Financial Interests, Personal and Institutional, Advisory Role: Ipsen; Financial Interests, Personal and Institutional, Invited Speaker: Roche. D. Lorente: Financial Interests, Personal and Institutional, Advisory Role: Janssen; Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: Bayer; Financial Interests, Personal and Institutional, Invited Speaker: Astellas; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Sponsor/Funding: Pfizer. J. Puente: Financial Interests, Personal and Institutional, Research Grant: Astellas; Financial Interests, Personal and Institutional, Advisory Role: Janssen; Financial Interests, Personal and Institutional, Advisory Role: MSD; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role: Bayer; Non-Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Eisai; Financial Interests, Personal and Institutional, Advisory Role: Ipsen; Financial Interests, Personal and Institutional, Invited Speaker: Sanofi; Financial Interests, Personal and Institutional, Invited Speaker: Roche; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Invited Speaker: Merck Serono; Financial Interests, Personal and Institutional, Invited Speaker: Pierre Fabre. P. Borrega: Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: Bayer; Financial Interests, Personal and Institutional, Advisory Role: Pfizer. F. Lopez Campos: Financial Interests, Personal and Institutional, Advisory Role: Astellas; Financial Interests, Personal and Institutional, Advisory Role: Janssen; Financial Interests, Personal and Institutional, Advisory Role: MSD. O. Fernandez Calvo: Financial Interests, Personal and Institutional, Advisory Role: Astellas; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: BMS; Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: EUSA; Financial Interests, Personal and Institutional, Invited Speaker: Pierre-Fabre; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Ipsen; Financial Interests, Personal and Institutional, Invited Speaker: Bayer; Financial Interests, Personal and Institutional, Invited Speaker: Janssen. R. Luque: Financial Interests, Personal and Institutional, Advisory Role: Astellas; Financial Interests, Personal and Institutional, Advisory Role: Janssen; Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: BMS; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: EUSA; Financial Interests, Personal and Institutional, Advisory Role: Novartis; Financial Interests, Personal and Institutional, Advisory Role: Ipsen. S. Ros Martínez: Financial Interests, Personal and Institutional, Advisory Role: Astellas; Financial Interests, Personal and Institutional, Advisory Role: Janssen; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role: MSD; Financial Interests, Personal and Institutional, Advisory Role: Bayer; Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: Eisai; Financial Interests, Personal and Institutional, Advisory Role: Ipsen; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Advisory Role: BMS. E. Castro: Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Research Grant: Janssen; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca. D. Olmos: Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Research Grant: Janssen; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca. All other authors have declared no conflicts of interest.