Real-world use of radium-223 for treatment of metastatic castration resistant-prostate cancer (mCRPC): results from the Dutch CAPRI registry

Date 30 September 2019
Event ESMO 2019 Congress
Session Poster Display session 3
Topics Prostate Cancer
Presenter Malou Kuppen
Citation Annals of Oncology (2019) 30 (suppl_5): v325-v355. 10.1093/annonc/mdz248
Authors M.C.P. Kuppen1, H.M. Westgeest2, A.J.M. van den Eertwegh3, J. Van Moorselaar4, N. Mehra5, J..L. Coenen6, I. van Oort7, A.C.M. van den Bergh8, J. Lavalaye9, K.K.H. Aben10, D.M. Somford11, R. de Wit12, A.M. Bergman13, C. Uyl-de Groot1, W.R. Gerritsen14
  • 1Institute For Medical Technology Assessment, Erasmus School of Health Policy and Management, 3062 PA - Rotterdam/NL
  • 2Internal Medicine, Amphia Ziekenhuis-location Langendijk, 4819 EV - Breda/NL
  • 3Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, 1081 HV - Amsterdam/NL
  • 4Urology, Amsterdam UMC, Vrije Universiteit, 1081 HV - Amsterdam/NL
  • 5Medical Oncology, Radboud University Medical Center, 6525 GA - Nijmegen/NL
  • 6Medical Oncology, Isala, 8025 AB - Zwolle/NL
  • 7Urology, Radboudumc, 6525 GA - Nijmegen/NL
  • 8Radiation Oncology, University Medical Center Groningen, 9713 GZ - Groningen/NL
  • 9Nuclear Medicine, St. Antonius Hospital, 3435 - Nieuwegein/NL
  • 10Department Of Research, Netherlands Comprehensive Cancer Organization, 6533AA - Nijmegen/NL
  • 11Urology, Canisius Wilhemina Ziekenhuis, 6532 SZ - Nijmegen/NL
  • 12Medical Oncology, Erasmus University Medical Center, 3000 CA - Rotterdam/NL
  • 13Division Of Internal Medicine (mod) And Oncogenomics, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 14Medical Oncology, Radboudumc, 6500 HB - Nijmegen/NL

Abstract

Background

Radium-223 dichloride (Ra-223) is a targeted alpha-emitter that selectively binds to areas of increased bone turnover in bone metastases. In the ALSYMPCA trial an increased overall survival over placebo in both docetaxel pretreated (14.4 mo) and docetaxel untreated (16.1 mo) patients was shown. With multiple life-prolonging agents (LPD), data on treatment sequencing and outcomes in real-world practice are needed. The aim of this study was to investigate the use of Ra-223 and outcomes in daily practice in the Netherlands.

Methods

Patients treated with Ra-223 in the CAPRI registry were included and followed until 01-01-2018. Subgroups were based on prior use of docetaxel (docetaxel naive, DOC-naïve; post-docetaxel, post-DOC). Outcomes were treatment sequence and overall survival from 1st Ra-223 injection.

Results

288 patients treated with Ra-223 were included in this analysis. 90% were pretreated with one or more lines of LPD (38% 1 line, 52% ≥1 line). 33% of DOC-naïve patients were treated with Ra-223 as line 1. Baseline characteristics are shown in the table. DOC-naïve patients had prognostic favorable baseline characteristics compared to post-DOC patients, namely higher hemoglobin (7.9 vs 7.4 mmol/L, p < 0.01), lower PSA (85 vs 147 µg/L, p < 0.01) and longer period from castration to mCRPC (16.8 vs 13.1 months, p < 0.01). 47% completed all 6 cycles. 43% were alive or lost-to-follow-up at database cutoff. Median overall survival was 12.2 months (IQR 7-24 months), with longer median overall survival in DOC-naïve compared to post-DOC patients (17.0 vs 11.2 months, p < 0.01).Table:

869P

Radium-223 N = 288Doc-naïve N = 120Post-doc N = 168p-value
Age ≥75 years (%)466333<0.01
Extent of disease (%) N0 / N1 / Nx M0 / M1 / Mx (visceral)54 / 20 / 26 71 / 4 / 2657 / 23 / 21 76 / 3 / 2152 / 18 / 30 67 / 4 / 290.62 0.78
Charlson score (%) 6 7-8 9-10 >1064 30 6 164 30 5 163 30 6 10.98
ECOG (%) 0 1 >1 Missing19 48 13 2024 43 13 1916 51 13 200.21
Hb, mmol/L Median (IQR) Missing (%)7.7 (6.8-8.3) 107.9 (7.1-8.4) 107.4 (6.6-8.1) 10<0.01
LDH, U/L Median (IQR) Missing (%)243 (201-310) 33240 (205-288) 31248 (197-332) 340.60
ALP, U/L Median (IQR) Missing (%)153 (91-267) 14139 (87-227) 14167 (94-274) 140.11
PSA, µg/L Median (IQR) Missing (%)124 (48-344) 1385 (44-205) 14147 (55-444) 13<0.01
Period from castration to mCRPC, months Median (IQR)14.3 (8-27)16.8 (9-28)13.1 (8-23)<0.01
Previous ART use, % Yes No80 2076 2483 170.12

ART, androgen-receptor targeting drugs (i.e. abiraterone acetate or enzalutamide)

Conclusions

Although Ra-223 was positioned as a later line of mCRPC in this Dutch real-world practice than in the ALSYMPCA trial, overall survival was comparable. This is probably explained by adequate patient selection. Further research on the best timing of Ra-223 in the treatment of mCRPC is awaited.

Clinical trial identification

NL3440 (NTR3591).

Editorial acknowledgement

Legal entity responsible for the study

Institute for Medical Technology Assessment, Erasmus University Rotterdam.

Funding

Sanofi-Aventis Netherlands B.V., Janssen-Cilag B.V., Astellas Pharma B.V., and Bayer B.V.

Disclosure

M.C.P. Kuppen: Travel / Accommodation / Expenses: Ipsen. H.M. Westgeest: Travel / Accommodation / Expenses: Ipsen; Honoraria (self): Roche. A.J.M. van den Eertwegh: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Merck. J. Van Moorselaar: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Sanofi-Genzyme. N. Mehra: Research grant / Funding (institution): Astellas; Honoraria (self), Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Sanofi; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self): Merck; Honoraria (self): Bayer; Honoraria (self): BMS; Honoraria (self): MSD. J.L. Coenen: Advisory / Consultancy: Sanofi. I. van Oort: Advisory / Consultancy, Research grant / Funding (self): Astellas; Advisory / Consultancy, Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy: Mdx health. D.M. Somford: Research grant / Funding (institution): Astellas. R. de Wit: Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy: Merck Sharp Dohme; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Janssen; Advisory / Consultancy: Clovis. A.M. Bergman: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Speaker Bureau / Expert testimony: Janssen. C. Uyl-de Groot: Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Janssen-Cilag; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Genzyme; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Glycostem Therapeutics; Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca. W.R. Gerritsen: Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Bavarian Nordic; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen-Cilag; Advisory / Consultancy: Amgen; Advisory / Consultancy: CureVac; Advisory / Consultancy: Dendreon; Advisory / Consultancy: Merck (MSD); Advisory / Consultancy: Morphosys; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Aglaia Biomedical Ventures; Advisory / Consultancy: PsiOxus Therapeutics. All other authors have declared no conflicts of interest.