Re-treatment with radium-223: 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases

Oliver Sartor, Daniel Heinrich, Neil Mariados, Maria José Méndez Vidal, Daniel Keizman, Camilla Thellenberg Karlsson, Avivit Peer, Giuseppe Procopio, Stephen J. Frank, Kalevi Pulkkanen, Eli Rosenbaum, Stefano Severi, José Trigo, Lucia Trandafir, Volker Wagner, Rui Li, Luke T. Nordquist

Research output: Contribution to journalArticle

Abstract

Background: Radium-223 dichloride (radium-223) is approved for patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open-label, phase 1/2 study NCT01934790 showed that re-treatment with radium-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2-year follow-up of the radium-223 re-treatment study. Methods: Patients with CRPC and bone metastases who completed 6 initial radium-223 injections with no disease progression in bone and later progressed were eligible for radium-223 re-treatment (up to 6 additional radium-223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium-223. Concomitant cytotoxic agents were not allowed during re-treatment but were allowed at the investigator's discretion during follow-up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate-specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-treatment start. Evaluation of safety and exploratory efficacy objectives included active 2-year follow-up. Safety results from active follow-up and updated efficacy are reported. Results: Overall, 44 patients were re-treated with radium-223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2-year active follow-up, during which no new safety concerns and no serious drug-related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months. Conclusions: Re-treatment with radium-223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up.

Original languageEnglish
Pages (from-to)1683-1691
Number of pages9
JournalProstate
Volume79
Issue number14
DOIs
Publication statusPublished - Jan 1 2019

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Radium
Bone Neoplasms
Castration
Prostatic Neoplasms
Neoplasm Metastasis
Disease-Free Survival
Safety
Injections
Therapeutics
Bone and Bones
Prostate-Specific Antigen
Alkaline Phosphatase
Disease Progression
Research Personnel
Survival
Cytotoxins
Drug-Related Side Effects and Adverse Reactions
Drug Therapy

Keywords

  • alkaline phosphatase
  • prostate-specific antigen
  • safety
  • SSEs
  • survival
  • symptomatic skeletal events

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Sartor, O., Heinrich, D., Mariados, N., Méndez Vidal, M. J., Keizman, D., Thellenberg Karlsson, C., ... Nordquist, L. T. (2019). Re-treatment with radium-223: 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases. Prostate, 79(14), 1683-1691. https://doi.org/10.1002/pros.23893

Re-treatment with radium-223 : 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases. / Sartor, Oliver; Heinrich, Daniel; Mariados, Neil; Méndez Vidal, Maria José; Keizman, Daniel; Thellenberg Karlsson, Camilla; Peer, Avivit; Procopio, Giuseppe; Frank, Stephen J.; Pulkkanen, Kalevi; Rosenbaum, Eli; Severi, Stefano; Trigo, José; Trandafir, Lucia; Wagner, Volker; Li, Rui; Nordquist, Luke T.

In: Prostate, Vol. 79, No. 14, 01.01.2019, p. 1683-1691.

Research output: Contribution to journalArticle

Sartor, O, Heinrich, D, Mariados, N, Méndez Vidal, MJ, Keizman, D, Thellenberg Karlsson, C, Peer, A, Procopio, G, Frank, SJ, Pulkkanen, K, Rosenbaum, E, Severi, S, Trigo, J, Trandafir, L, Wagner, V, Li, R & Nordquist, LT 2019, 'Re-treatment with radium-223: 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases', Prostate, vol. 79, no. 14, pp. 1683-1691. https://doi.org/10.1002/pros.23893
Sartor, Oliver ; Heinrich, Daniel ; Mariados, Neil ; Méndez Vidal, Maria José ; Keizman, Daniel ; Thellenberg Karlsson, Camilla ; Peer, Avivit ; Procopio, Giuseppe ; Frank, Stephen J. ; Pulkkanen, Kalevi ; Rosenbaum, Eli ; Severi, Stefano ; Trigo, José ; Trandafir, Lucia ; Wagner, Volker ; Li, Rui ; Nordquist, Luke T. / Re-treatment with radium-223 : 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases. In: Prostate. 2019 ; Vol. 79, No. 14. pp. 1683-1691.
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abstract = "Background: Radium-223 dichloride (radium-223) is approved for patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open-label, phase 1/2 study NCT01934790 showed that re-treatment with radium-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2-year follow-up of the radium-223 re-treatment study. Methods: Patients with CRPC and bone metastases who completed 6 initial radium-223 injections with no disease progression in bone and later progressed were eligible for radium-223 re-treatment (up to 6 additional radium-223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium-223. Concomitant cytotoxic agents were not allowed during re-treatment but were allowed at the investigator's discretion during follow-up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate-specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-treatment start. Evaluation of safety and exploratory efficacy objectives included active 2-year follow-up. Safety results from active follow-up and updated efficacy are reported. Results: Overall, 44 patients were re-treated with radium-223; 29 (66{\%}) completed all 6 injections, and 34 (77{\%}) entered 2-year active follow-up, during which no new safety concerns and no serious drug-related adverse events were noted. rPFS events (progression or death) occurred in 19 (43{\%}) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11{\%}) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months. Conclusions: Re-treatment with radium-223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up.",
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TY - JOUR

T1 - Re-treatment with radium-223

T2 - 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases

AU - Sartor, Oliver

AU - Heinrich, Daniel

AU - Mariados, Neil

AU - Méndez Vidal, Maria José

AU - Keizman, Daniel

AU - Thellenberg Karlsson, Camilla

AU - Peer, Avivit

AU - Procopio, Giuseppe

AU - Frank, Stephen J.

AU - Pulkkanen, Kalevi

AU - Rosenbaum, Eli

AU - Severi, Stefano

AU - Trigo, José

AU - Trandafir, Lucia

AU - Wagner, Volker

AU - Li, Rui

AU - Nordquist, Luke T.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Radium-223 dichloride (radium-223) is approved for patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open-label, phase 1/2 study NCT01934790 showed that re-treatment with radium-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2-year follow-up of the radium-223 re-treatment study. Methods: Patients with CRPC and bone metastases who completed 6 initial radium-223 injections with no disease progression in bone and later progressed were eligible for radium-223 re-treatment (up to 6 additional radium-223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium-223. Concomitant cytotoxic agents were not allowed during re-treatment but were allowed at the investigator's discretion during follow-up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate-specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-treatment start. Evaluation of safety and exploratory efficacy objectives included active 2-year follow-up. Safety results from active follow-up and updated efficacy are reported. Results: Overall, 44 patients were re-treated with radium-223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2-year active follow-up, during which no new safety concerns and no serious drug-related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months. Conclusions: Re-treatment with radium-223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up.

AB - Background: Radium-223 dichloride (radium-223) is approved for patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open-label, phase 1/2 study NCT01934790 showed that re-treatment with radium-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2-year follow-up of the radium-223 re-treatment study. Methods: Patients with CRPC and bone metastases who completed 6 initial radium-223 injections with no disease progression in bone and later progressed were eligible for radium-223 re-treatment (up to 6 additional radium-223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium-223. Concomitant cytotoxic agents were not allowed during re-treatment but were allowed at the investigator's discretion during follow-up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate-specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-treatment start. Evaluation of safety and exploratory efficacy objectives included active 2-year follow-up. Safety results from active follow-up and updated efficacy are reported. Results: Overall, 44 patients were re-treated with radium-223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2-year active follow-up, during which no new safety concerns and no serious drug-related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months. Conclusions: Re-treatment with radium-223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up.

KW - alkaline phosphatase

KW - prostate-specific antigen

KW - safety

KW - SSEs

KW - survival

KW - symptomatic skeletal events

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U2 - 10.1002/pros.23893

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