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
5105 - Fresh blood Immune cell monitoring in patients treated with nivolumab in the GETUG-AFU26 NIVOREN study: association with toxicity and treatment outcome
Presenter: Aude DESNOYER
Session: Poster Display session 3
Resources:
Abstract
1877 - Advanced clear-cell renal cell carcinoma (accRCC): association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome.
Presenter: Annelies Verbiest
Session: Poster Display session 3
Resources:
Abstract
5543 - Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
Presenter: Valerio Iebba
Session: Poster Display session 3
Resources:
Abstract
2689 - mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
Presenter: Cristina Suarez Rodriguez
Session: Poster Display session 3
Resources:
Abstract
3069 - Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in Advanced Renal Cell Carcinoma (RCC)
Presenter: Aly-Khan Lalani
Session: Poster Display session 3
Resources:
Abstract
5089 - Finding the Right Biomarker for Renal Cell Carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response.
Presenter: Lorena Incorvaia
Session: Poster Display session 3
Resources:
Abstract
2594 - Algorithms derived from quantitative pathology can be a gatekeeper in patient selection for clinical trials in localised clear cell renal cell carcinoma (ccRCC)
Presenter: In Hwa Um
Session: Poster Display session 3
Resources:
Abstract
2566 - High baseline blood volume is an independent favorable prognostic factor for overall and progression-free survival in patients with metastatic renal cell carcinoma
Presenter: Aska Drljevic-nielsen
Session: Poster Display session 3
Resources:
Abstract
2675 - Impact of estimand selection on adjuvant treatment outcomes in renal cell carcinoma (RCC)
Presenter: Daniel George
Session: Poster Display session 3
Resources:
Abstract
1541 - TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Presenter: Bozo Kruslin
Session: Poster Display session 3
Resources:
Abstract