Abstract 3816
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 = 288 | Doc-naïve N = 120 | Post-doc N = 168 | p-value | |
---|---|---|---|---|
Age ≥75 years (%) | 46 | 63 | 33 | <0.01 |
Extent of disease (%) N0 / N1 / Nx M0 / M1 / Mx (visceral) | 54 / 20 / 26 71 / 4 / 26 | 57 / 23 / 21 76 / 3 / 21 | 52 / 18 / 30 67 / 4 / 29 | 0.62 0.78 |
Charlson score (%) 6 7-8 9-10 >10 | 64 30 6 1 | 64 30 5 1 | 63 30 6 1 | 0.98 |
ECOG (%) 0 1 >1 Missing | 19 48 13 20 | 24 43 13 19 | 16 51 13 20 | 0.21 |
Hb, mmol/L Median (IQR) Missing (%) | 7.7 (6.8-8.3) 10 | 7.9 (7.1-8.4) 10 | 7.4 (6.6-8.1) 10 | <0.01 |
LDH, U/L Median (IQR) Missing (%) | 243 (201-310) 33 | 240 (205-288) 31 | 248 (197-332) 34 | 0.60 |
ALP, U/L Median (IQR) Missing (%) | 153 (91-267) 14 | 139 (87-227) 14 | 167 (94-274) 14 | 0.11 |
PSA, µg/L Median (IQR) Missing (%) | 124 (48-344) 13 | 85 (44-205) 14 | 147 (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 No | 80 20 | 76 24 | 83 17 | 0.12 |
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.
Resources from the same session
3630 - Results of phase 1 clinical trial of high doses of Seleno-L-methionine (SLM) in sequential combination with Axitinib in previously treated and relapsed clear cell renal carcinoma (ccRCC) patients
Presenter: Yousef Zakharia
Session: Poster Display session 3
Resources:
Abstract
2356 - Safety and Efficacy of CDX-014 , an Antibody-Drug Conjugate against T Cell immunoglobulin mucin-1 (TIM-1), in advanced Renal Cell Carcinoma
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
1028 - SPAZO2 (SOGUG): Outcomes and prognostic significance of IMDC intermediate prognosis subclassification in metastatic renal cell carcinoma (mRCC) in patients treated with 1st-line pazopanib (1stPz).
Presenter: Begona P. Valderrama
Session: Poster Display session 3
Resources:
Abstract
2293 - Effect of Antacid Intake on the Therapeutic Efficacy of Sunitinib (SUN) in Metastatic Renal Cell Carcinoma (mRCC) Patients (pts): a Sub-Analysis of the STAR-TOR Registry
Presenter: Katrin Schlack
Session: Poster Display session 3
Resources:
Abstract
1451 - Randomized phase 3 trial of avelumab + axitinib vs sunitinib as first-line treatment for advanced renal cell carcinoma: JAVELIN Renal 101 Japanese subgroup analysis
Presenter: Motohide Uemura
Session: Poster Display session 3
Resources:
Abstract
4399 - Overall and progression-free survival according to MSKCC scores in 1st line sunitinib treatment of metastatic renal cell carcinoma (mRCC)
Presenter: Jindrich Finek
Session: Poster Display session 3
Resources:
Abstract
1344 - Combination therapy with checkpoint inhibitors for first-line treatment of advanced renal cell carcinoma: A systematic review and meta-analysis of randomized controlled trials
Presenter: Kyaw Thein
Session: Poster Display session 3
Resources:
Abstract
3462 - A phase II trial of TKI induction followed by a randomized comparison between nivolumab or TKI continuation in renal cell carcinoma (NIVOSWITCH)
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract
5268 - Nivolumab (N) treatment beyond progression in a real-world cohort of patients (pts) with metastatic renal cell carcinoma (mRCC)
Presenter: Sophie Hans
Session: Poster Display session 3
Resources:
Abstract
4235 - First results of safety profile of nivolumab (NIVO) in combination with stereotactic body radiotherapy (SBRT) in II and III line of patients (pts) with metastatic renal cell carcinoma (mRCC) in NIVES Study
Presenter: Cristina Masini
Session: Poster Display session 3
Resources:
Abstract