scholarly journals Concurrent or layered treatment with radium-223 and enzalutamide or abiraterone/prednisone: real-world clinical outcomes in patients with metastatic castration-resistant prostate cancer

2020 ◽  
Vol 23 (4) ◽  
pp. 680-688
Author(s):  
Neal Shore ◽  
Celestia S. Higano ◽  
Daniel J. George ◽  
Cora N. Sternberg ◽  
Fred Saad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real World ◽  
Incidence Rates ◽  
Castration Resistant Prostate Cancer ◽  
Real World Data ◽  
Combination Treatments ◽  
Castration Resistant ◽  
Radium 223 ◽  
Pathologic Fractures ◽  
Health Database

Abstract Background In this study, we evaluated real-world data on radium-223 plus abiraterone/prednisone or enzalutamide. Previously, the ERA 223 trial (NCT02043678) demonstrated increased fracture risk with concurrent treatment with radium-223 and abiraterone plus prednisone/prednisolone in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods We used the Flatiron Health database to perform a retrospective study of patients with mCRPC treated with radium-223. Treatment with radium-223 plus abiraterone/prednisone or enzalutamide was defined as concurrent if both drugs started within 30 days of one another, or layered when the second drug started ≥30 days after the first. The index date was defined as the day of the first radium-223 dose. Outcome measures included symptomatic skeletal events (SSEs), overall survival (OS), and patterns of treatments received. Results Of the 625 patients treated with radium-223, 22% received it together with abiraterone/prednisone and 27% with enzalutamide. When these agents were combined, they were often initiated in a layered fashion (73% layered, 23% concurrent). Prior or concomitant bone health agents (BHAs) were received by 67% and 55% of patients, respectively. Median follow-up was 9 months. Overall, incidence rates for SSEs and pathologic fractures were 0.35 and 0.11 patients per person-year, respectively. Median OS from mCRPC diagnosis was 28.1 months. Conclusions In this real-world setting, combination treatments with radium-223 and abiraterone/prednisone or enzalutamide were common. These agents were more commonly given in a layered than a concurrent fashion. Incidence rates for SSEs were reduced when BHAs were used; however, BHAs were underutilized.

A retrospective analysis of treatment patterns in metastatic castration-resistant prostate cancer patients treated with radium-223.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 180-180 ◽  
Author(s):  
A. Oliver Sartor ◽  
Sreevalsa Appukkuttan ◽  
Ronald E. Aubert ◽  
Jeffrey Weiss ◽  
Joy Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real World ◽  
Pilot Trial ◽  
Clinical Trial Data ◽  
Castration Resistant Prostate Cancer ◽  
Real World Data ◽  
Data Set ◽  
World Data ◽  
Castration Resistant ◽  
Radium 223

180 Background: Radium-223 (RA-223) is the first FDA approved targeted alpha therapy that significantly improves overall survival (OS) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) with symptomatic bone metastases. There is limited real world data describing RA-223 current use. Methods: A retrospective patient chart review was done of men who received at least 1 cycle of Ra-223 for mCRPC in 10 centers throughout the US (4 academic, 6 private practices). All pts had a minimum follow-up of 4 months, or placed in hospice or death. Descriptive analyses for clinical characteristics and treatment outcomes were performed. Results: Among the 200 pts (mean age-73.6 years, mean Charlson comorbidity index-6.9) RA-223 was initiated on average 1.6 years from mCRPC diagnosis (first line use (1L)=38.5%, 2L=31.5% and ≥3L=30%). 78% completed 5-6 cycles of RA-223 with mean therapy duration of 4.2 months. Among all pts, 43% received RA-223 as monotherapy (no overlap with other mCRPC therapies) while 57% had combination therapy with either abiraterone or enzalutamide. Median OS following RA-223 initiation was 21.2 months (95% CI 19.6- 29.2). Table provides the RA-223 utilization by type of clinical practice. Conclusions: Utilization of RA-223 in this real world data set was distinct from clinical trial data. Most patients received RA-223 in combination with abiraterone or enzalutamide, therapies that were unavailable when the pilot trial was conducted. Median survival was 21.2 months. Real world use of RA-223 has evolved as newer agents have become FDA approved in bone-metastatic CRPC. Academic and community patterns of practice were more similar than distinct. [Table: see text]

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

2019 ◽  
Vol 30 ◽  
pp. v340
Author(s):  
M.C.P. Kuppen ◽  
H.M. Westgeest ◽  
A.J.M. van den Eertwegh ◽  
J. Van Moorselaar ◽  
N. Mehra ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real World ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223

Randomized phase II study evaluating the addition of pembrolizumab to radium-223 in metastatic castration-resistant prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 98-98
Author(s):  
Atish Dipankar Choudhury ◽  
Lucia Kwak ◽  
Alexander Cheung ◽  
Abhishek Tripathi ◽  
Amanda Fredericks Pace ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cell ◽  
Cd8 T Cell ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Cell Infiltrate ◽  
Castration Resistant ◽  
Radium 223 ◽  
Pathologic Fractures ◽  
Bone Biopsies

98 Background: Treatment (tx) options for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) to bone are limited. Radium-223 (R223) has demonstrated overall survival (OS) benefit, but objective clinical responses to R223 or the anti-PD1 checkpoint inhibitor (CPI) pembrolizumab (pem) are infrequent. As R223 may increase immunogenicity of mCRPC to bone and increase activity of CPI, we undertook a Phase 2 study to assess safety of the combination and differences in immune cell infiltrate in bone biopsies (bx) and preliminary clinical activity of R223 + pem vs. R223 alone. Methods: Eligibility required mCRPC to bone with no visceral metastases (mets) or lymph nodes > 2 cm, ECOG PS 0 or 1, Hgb ≥ 9 g/dL, and no prior R223 or CPI. Pts underwent bone bx at screening and at 8 wks. Pts were stratified by alkaline phosphatase ≥220 vs. < 220 U/L and high vs. low volume bony mets (CHAARTED criteria) and randomized 2:1 to receive R223 55 kBq/kg q4wks + pem 200 mg q3wks (Arm A) or R223 55 kBq/kg q4wks alone (Arm B). If restaging after 3 doses R223 showed at least stable disease, pts in Arm A continued pem alone until progressive disease (PD). Upon PD, R223 was resumed if no new visceral mets. Pts continued tx until clinical/radiologic PD, unacceptable toxicity or completion of 6 R223 doses. The primary endpoint was difference in CD4+ and CD8+ T-cell infiltrate in 8 wk vs. baseline bx; secondary endpoints were safety/tolerability, radiographic progression-free survival (rPFS) and OS. Exploratory endpoints included PSA response and rate of symptomatic skeletal events (SSEs). Results: Of 45 pts enrolled, 42 received study tx (29 Arm A, 13 Arm B) and were eligible for analysis. 21 pts in Arm A and 5 in Arm B had evaluable paired bone bx. Median fold-change of proportion of CD4+ T-cells/total cell count from baseline to 8 wks was 0.90 (range 0.0-26.6) in Arm A and 0.40 (0.0-13.0) in Arm B (P = 0.87); for CD8+ cells, median 0.67 (0.0-40.4) in Arm A and 0.40 (0.1-28.8) in Arm B (P = 0.77). Grade 3 treatment-related non-hematologic adverse events (AEs) occurred in 3 pts (10%) in Arm A (pneumonitis, diarrhea, AST increased); none in Arm B. Median rPFS was 6.7 mo (95% CI 2.7-11.0 mo) in Arm A and 5.7 mo (2.6-NR) in Arm B. Median OS was 16.9 mo (12.7-NR) in Arm A and 16.0 mo (9.0-NR) in Arm B. 3 pts (10%) in Arm A and 0 in Arm B had PSA reduction of ≥ 50%. SSE rate was 38% in Arm A and 54% in Arm B, with pathologic fractures in 0% of pts in Arm A and 23% in Arm B. Conclusions: In the 62% of treated pts with evaluable paired bx at baseline and after 8 wks, there was no evidence of increased CD4+ or CD8+ T-cell infiltration with R223 + pem. Additional biomarker analyses will be presented. This study revealed that R233 + pem did not result in unexpected AEs, but did not lead to prolonged rPFS or OS compared to R223 alone to support this two-drug combination in a biomarker-unselected population in this setting. Clinical trial information: NCT03093428.

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