Radium-223 chloride impact on skeletal-related events in patients with castration-resistant prostate cancer (CRPC) with bone metastases: A phase III randomized trial (ALSYMPCA).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 9-9 ◽  
Author(s):  
A. Oliver Sartor ◽  
Daniel Heinrich ◽  
Svein Inge Helle ◽  
Joe M. O'Sullivan ◽  
Sophie D. Fossa ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Standard Of Care ◽  
High Energy ◽  
Alpha Particles ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Radium 223 ◽  
Skeletal Related Events ◽  
Favorable Safety

9 Background: Radium-223 chloride (Ra-223) is a 1st-in-class alpha-pharmaceutical targeting bone metastases (mets) with high-energy alpha-particles of short range (<100 μm). ALSYMPCA, a phase III, double-blind, randomized, multinational study, compared Ra-223 plus best standard of care (BSC) vs placebo (pbo) plus BSC in patients (pts) with bone mets in CRPC. The primary endpoint was OS; secondary endpoints included skeletal-related events (SREs). Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets on scintigraphy and no known visceral mets; were receiving BSC; and either previously received docetaxel, were docetaxel ineligible, or refused docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra‐223 (50 kBq/kg IV) q4 wks or matching pbo and stratified by prior docetaxel use, baseline alkaline phosphatase level, and current bisphosphonate use. Results: 922 pts (Ra-223, n = 615; pbo, n = 307) were randomized from 6/2008-2/2011. Based on data from a planned interim analysis (n = 809), unblinded June 2011, Ra-223 significantly improved OS in pts with CRPC with bone mets vs pbo (median OS 14.0 vs 11.2 mo, respectively; two-sided P = 0.00185; HR = 0.695; 95% CI, 0.552-0.875). SREs were lower in the Ra-223 vs pbo group, and time to 1st SRE was significantly delayed (median time to SRE 13.6 mo vs 8.4 mo, respectively; P = .00046; HR = .610; 95% CI, .461-.807). Conclusions: Ra-223 significantly delayed time to 1st SRE and SRE components, except surgical intervention. These reductions in SREs, particularly SCC, are noteworthy. Ra-223 is an effective therapy with a highly favorable safety profile and may provide a new standard of care for treatment of CRPC pts with bone mets. [Table: see text]

Radium-223 chloride (Ra-223) impact on skeletal-related events (SREs) and ECOG performance status (PS) in patients with castration-resistant prostate cancer (CRPC) with bone metastases: Interim results of a phase III trial (ALSYMPCA).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4551-4551 ◽  
Author(s):  
A. Oliver Sartor ◽  
Daniel Heinrich ◽  
Joe M. O'Sullivan ◽  
Sophie D. Fossa ◽  
Ales Chodacki ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Performance Status ◽  
Standard Of Care ◽  
High Energy ◽  
Alpha Particles ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Radium 223 ◽  
Ecog Ps

4551 Background: Ra-223, a 1st-in-class alpha-pharmaceutical, targets bone metastases (mets) with high-energy alpha-particles of short range (<100 μm). ALSYMPCA, a phase III, double-blind, randomized, multinational study, compared Ra-223 plus best standard of care (BSC) v placebo (pbo) plus BSC in patients (pts) with bone mets in CRPC. The primary endpoint was OS; secondary endpoints included SREs and ECOG PS. Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets on scintigraphy and no known visceral mets; were receiving BSC; and either previously received docetaxel, were docetaxel ineligible, or refused docetaxel. Pts were randomized 2:1 to 6 injections of Ra‑223 (50 kBq/kg IV) q4 wks or matching pbo and stratified by prior docetaxel use, baseline ALP level, and current bisphosphonate use. Results: 921 pts were randomized from 6/2008-2/2011. In a planned interim analysis (n = 809), Ra-223 significantly improved OS v pbo (median OS 14.0 v 11.2 mo, respectively; two-sided P = .00185; HR = .695; 95% CI, .552-.875).SREs were lower in the Ra-223 v pbo group, and time to 1st SRE was significantly delayed (median time to SRE 13.6 mo v 8.4 mo, respectively; P = .00046; HR = .610; 95% CI, .461-.807). The proportion of pts with ECOG PS deterioration (≥ 2 points) was less in Ra-223 v pbo group at Wk 12 and Wk 24 (4%, 15/389 v 9%, 16/180 and 7%, 16/236 v 12%, 10/83, respectively). Time to ECOG PS deterioration (≥ 2 points) was significantly delayed by Ra-223 v pbo (P = .003; HR = .62; 95% CI, .46-.85). Conclusions: Ra-233 significantly delayed time to 1st SRE and SRE components, notably SCC. Fewer pts in the Ra-223 group had ECOG PS deterioration. Ra-223 improves OS with excellent safety and may provide a new standard of care for CRPC pts with bone mets. [Table: see text]

Updated analysis of radium-223 dichloride (Ra-223) impact on skeletal-related events (SRE) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase III randomized trial (ALSYMPCA).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 11-11 ◽  
Author(s):  
Nicholas J. Vogelzang ◽  
Chris Parker ◽  
Sten Nilsson ◽  
Robert Edward Coleman ◽  
C. Gillies O'Bryan-Tear ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Standard Of Care ◽  
High Energy ◽  
Alpha Particles ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Median Increase ◽  
Radium 223 ◽  
Delayed Time

11 Background: Ra-223 is a first-in-class alpha-pharmaceutical targeting bone metastases (mets) with high-energy, short-range (< 100 μm) alpha-particles. In the phase 3, double-blind, randomized, multinational ALSYMPCA study, Ra-223 significantly improved OS in CRPC patients (pts) with bone mets by a median increase of 3.6 months compared with placebo (median OS: 14.9 vs 11.3 mo; P < 0.001; HR = 0.69; 95% CI: 0.58-0.83). An updated analysis of the SRE secondary endpoint is presented. Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets on scintigraphy and no known visceral mets; were receiving best standard of care (BSoC); and either previously received docetaxel, or did not because they were docetaxel ineligible, or refused docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra‑223 (50 kBq/kg IV) q4wk or matching placebo and stratified by prior docetaxel use, baseline alkaline phosphatase level, and current bisphosphonate use. Results: 921 pts were randomized (Ra-223, n = 614; placebo, n = 307); 40% had >20 mets. Ra-223 significantly delayed time to first SRE versus placebo by a median increase of 5.8 months (median time to SRE: 15.6 vs 9.8 mo; P < 0.001; HR = 0.66; 95% CI: 0.52-0.83). Ra-223 also reduced the risk of time to first event for all 4 SRE components versus placebo. Conclusions: Ra-223 significantly delayed time to first SRE with a reduction in risk observed for all 4 SRE components. Despite the longer time at risk, Ra-223 patients had an approximately 50% reduction in risk for SCC. Ra-223 is an effective therapy with a highly favorable safety profile and may provide a new standard of care for treatment of CRPC pts with bone mets. Clinical trial information: NCT00699751. [Table: see text]

Updated analysis of the phase III, double-blind, randomized, multinational study of radium-223 chloride in castration-resistant prostate cancer (CRPC) patients with bone metastases (ALSYMPCA).

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA4512-LBA4512 ◽  
Author(s):  
Chris Parker ◽  
Sten Nilsson ◽  
Daniel Heinrich ◽  
Joe M. O'Sullivan ◽  
Sophie D. Fossa ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Standard Of Care ◽  
High Energy ◽  
Phase Iii ◽  
Multinational Study ◽  
Double Blind ◽  
Risk Of Death ◽  
Radium 223 ◽  
Alpha Emitter ◽  
Secondary Endpoints

LBA4512 Background: Radium-223 chloride (Ra-223), a targeted alpha-emitter, targets bone metastases (mets) with high-energy alpha-particles of short range (<100 µm). ALSYMPCA, a phase III double-blind, randomized, multinational study, compared Ra-223 plus best standard of care (BSC) vs placebo plus BSC in CRPC patients (pts) with bone mets. In a planned interim analysis (n = 809), based on 314 events, Ra-223 significantly improved overall survival (OS) vs placebo (median 14.0 mo vs 11.2 mo, respectively; HR = .695; 95% CI, .552-.875; 2-sided p = .00185). Secondary endpoints were met and Ra-223 safety was favorable. An updated analysis was conducted prior to the crossover to further assess the effect of Ra-223 on the primary endpoint (OS), secondary endpoints including skeletal-related events (SREs), and safety. Methods: Eligible pts had confirmed symptomatic CRPC with ≥ 2 bone mets; no known visceral mets; and were post-docetaxel, unfit for docetaxel, or had declined docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra-223 (50 kBq/kg IV) q4wks or matching placebo. An updated descriptive analysis of OS, based on 528 events, was performed including data from all randomized pts prior to implementing crossover to Ra-223 for placebo pts. Results: 921 pts (Ra-223, n = 614; placebo, n = 307) were randomized from 6/2008-2/2011. Ra‑223 significantly improved OS vs placebo (median 14.9 mo vs 11.3 mo, respectively; HR = .695; 95% CI, .581-.832; p = 0.00007), and time to first SRE was significantly prolonged (median 15.6 mo vs 9.8 mo, respectively; HR = 0.658; 95% CI, 0.522-0.830; p = 0.00037). Safety and tolerability of Ra-223 remained favorable, with low myelosuppression (e.g., gr 3/4 neutropenia in 2.2% and 0.7% and gr 3/4 thrombocytopenia in 6.3% and 2% of the Ra-223 and placebo groups, respectively). Conclusions: On updated analysis, the median OS benefit for Ra-223 increased from 2.8 to 3.6 months, with a hazard ratio of 0.695 (i.e., 30.5% reduction in risk of death). Ra-223 is an effective therapy that improves OS and time to first SRE with a highly favorable safety profile, and may provide a new standard of care for CRPC pts with bone mets.

Overall survival benefit and safety profile of radium-223 chloride, a first-in-class alpha-pharmaceutical: Results from a phase III randomized trial (ALSYMPCA) in patients with castration-resistant prostate cancer (CRPC) with bone metastases.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 8-8 ◽  
Author(s):  
Chris Parker ◽  
Daniel Heinrich ◽  
Joe M. O'Sullivan ◽  
Sophie D. Fossa ◽  
Ales Chodacki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bone Metastases ◽  
Survival Data ◽  
Safety Profile ◽  
Standard Of Care ◽  
High Energy ◽  
Phase Iii ◽  
Rank Test ◽  
Data Set ◽  
Radium 223

8 Background: Radium-223 chloride (Ra-223) is a first-in-class alpha-pharmaceutical targeting bone metastases (mets) with high-energy alpha-particles of extremely short range (<100 μm). ALSYMPCA, a phase III, double-blind, randomized, multinational study, compared efficacy, in terms of overall survival (OS), and safety of Ra-223 plus best standard of care (BSC) vs placebo plus BSC in patients (pts) with bone mets in CRPC. Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets on scintigraphy and no known visceral mets; were receiving BSC; and either previously received docetaxel, were docetaxel ineligible, or refused docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra‐223 (50 kBq/kg IV) q4 wks or matching placebo and stratified by prior docetaxel use, baseline alkaline phosphatase level, and current bisphosphonate use. A planned interim analysis (IA) was conducted to assess the effect of Ra-223 on the primary endpoint (OS) using a predefined threshold. Survival data were compared using a stratified log-rank test. Results: 922 pts (Ra-223, n = 615; placebo, n = 307) were randomized from 6/2008-2/2011. 445 (58%) of 809 pts in the IA data set received prior treatment with docetaxel. Ra-223 significantly improved OS in pts with CRPC with bone mets vs placebo (two-sided P = 0.00185; HR = 0.695; 95% CI, 0.552-0.875; median OS 14.0 mo vs 11.2 mo, respectively). Safety and tolerability of Ra-223 were highly favorable and showed low incidence of myelosuppression (eg, grades 3/4 neutropenia in 1.8% and 0.8% and thrombocytopenia in 4% and 2% of the Ra-223 and placebo groups, respectively). Conclusions: Ra-223 is an effective therapy that improved OS with a highly favorable safety profile, and may provide a new standard of care for the treatment of CRPC pts with bone mets. [Table: see text]

Efficacy and safety of radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases who did or did not receive prior docetaxel (D) in the phase III ALSYMPCA trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5068-5068
Author(s):  
Nicholas J. Vogelzang ◽  
Svein Inge Helle ◽  
Dag Clement Johannessen ◽  
Joe M. O'Sullivan ◽  
Jose E. Garcia-Vargas ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Survival Data ◽  
Safety Profile ◽  
Phase Iii ◽  
Rank Test ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Favorable Safety Profile ◽  
Radium 223 ◽  
Favorable Safety

5068 Background: Ra-223, a first-in-class α-emitter, significantly improved median overall survival (OS) by 3.6 mo vs placebo (Pbo) in CRPC patients (pts) with bone metastases (mets) receiving best standard of care (BSoC) in the ALSYMPCA study (HR = 0.695; 95% CI, 0.581-0.832; p = 0.00007), and had a highly favorable safety profile in the updated ALSYMPCA analysis (Parker et al. ASCO 2012). This predefined subgroup analysis assessed efficacy and safety of Ra-223 in pts who did or did not receive prior D (pD). Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets; had no known visceral mets; were receiving BSoC; and had received pD, or were unfit for or declined D (npD). Pts were randomized 2:1 to 6 injections of Ra-223 (50 kBq/kg IV) q4wk or matching Pbo and stratified by prior D use, baseline alkaline phosphatase level, and current bisphosphonate use. Survival data were compared using a log-rank test. Results: 395/921 (43%) randomized pts had npD (Ra-223, n = 262; Pbo, n = 133); 526/921 (57%) received pD (Ra-223, n = 352; Pbo, n = 174). Median ages were 74 y (npD) and 69 y (pD). In pts with npD, median OS was 16.1 mo in the Ra-223 group vs 11.5 mo in the Pbo group (HR = 0.745; 95% CI, 0.562-0.987; p = 0.039). In pts with pD, median OS was 14.4 mo vs 11.3 mo in the Ra-223 and Pbo groups, respectively (HR = 0.710; 95% CI, 0.565-0.891; p = 0.003). Overall, there was a low incidence of myelosuppression. Incidences of neutropenia and thrombocytopenia were higher in pts with pD vs pts with npD. Conclusions: Ra-223 significantly prolonged OS and had a highly favorable safety profile in CRPC pts with bone mets, regardless of whether they had pD or npD. pD pts had a slightly increased rate of grade 3 and 4 bone marrow suppression with Ra-223. Clinical trial information: NCT00699751. [Table: see text]

Alkaline phosphatase (ALP) normalization and overall survival in patients with bone metastases from castration-resistant prostate cancer (CRPC) treated with radium-223.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 49-49 ◽  
Author(s):  
C. Parker ◽  
C. G. O'Bryan-Tear ◽  
B. Bolstad ◽  
A. Lokna ◽  
S. Nilsson
Keyword(s):  
Overall Survival ◽  
Bone Metastases ◽  
High Energy ◽  
Serum Markers ◽  
Phase Iii ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Phase Ii Studies ◽  
Randomized Phase Ii

49 Background: Radium-223 (Alpharadin) is a first-in-class alpha-pharmaceutical. It targets bone metastases with high-energy alpha-radiation of extremely short range that spares bone marrow. Radium-223 has a profound effect on serum markers of bone metabolism, including ALP, in patients with bone metastases from CRPC. In an exploratory analysis, we studied whether this effect is associated with a meaningful clinical benefit. Methods: Patients with CRPC and bone metastases were treated in 2 randomized phase II studies. BC1-02 was a placebo-controlled study of radium-223 (50 kBq/kg) every 4 weeks for 12 weeks. BC1-04 evaluated radium-223 (25, 50, or 80 kBq/kg) every 6 weeks for 12 weeks. Baseline total ALP values > 128 U/L were considered elevated; those decreasing to below 128 U/L during treatment with radium-223 were defined as normalized, and those remaining above that value as non-normalized. Results: In BC1-02, ALP normalization was seen in 12/26 (46%) patients treated with radium-223. Median survivals of those with and without ALP normalization were 102 weeks and 42 weeks, respectively (log-rank P < 0.001). In BC1-04, ALP normalization was seen in 25/75 (33%) cases: 5/29 (17%) in the 25 kBq/kg group, 10/25 (40%) with 50 kBq/kg, and 10/21 (48%) with 80 kBq/kg, indicating a dose-response relationship. Median survivals for the 25 patients with, and the 50 patients without, ALP normalization were 102 weeks and 58 weeks, respectively (log-rank P = 0.0086). Conclusions: Inpatients with metastatic CRPC and bone metastases treated with radium-223, ALP normalization was associated with significantly better overall survival. These data support the rationale for the ongoing ALSYMPCA phase III trial of radium-223. [Table: see text]

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