1. Retreatment With Radium-223 Safe, Showing Activity in Patients With CRPC and Bone Metastases
CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
CRPC, castration-resistant prostate cancer.
This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

2. Radium-223 Retreatment in CRPC: Study Background
Radium-223: alpha-emitting radiopharmaceutical that exerts potent cytotoxic effects on bone metastases
In phase III ALSYMPCA trial, improved OS by 3.6 mos (P < .001), delayed time to first symptomatic skeletal event by 5.8 mos (P < ), and had favorable safety profile for CRPC pts with bone metastases[1,2]
Outcomes based on one 50-kBq/kg injection Q4W for 6 injections[1,2]
Data suggest radium-223 retreatment may provide added benefit to pts who received initial 6-injection course[3]
Current international, prospective, open-label phase I/II study evaluated efficacy and safety of radium-223 retreatment in pts with CRPC and bone metastases[4]
CRPC, castration-resistant prostate cancer.
1. Parker C, et al. N Engl J Med. 2013;369: Sartor O, et al. Lancet Oncol. 2014;15: Sartor O, et al. ASCO GU Abstract Sartor O, et al. ASCO Abstract 5074.
Slide credit: clinicaloptions.com

3. Radium-223 Retreatment in CRPC: Study Design
Pts (N = 44) with metastatic CRPC who experienced radiographic or clinical progression following initial radium-223 treatment enrolled January 2014 to June 2015
Second 6-injection course of radium kBq/kg Q4W administered > 30 days after end of initial course
Pts actively followed up to 2 yrs after last radium-223 injection, with long- term follow up carried out to 7 yrs
Primary endpoint: safety
Exploratory endpoints: time to radiographic bone progression, radiographic PFS, OS, time to first SSE, SSE-free survival, time to pain progression
Findings from this study compared with those from phase III ALSYMPCA trial
CRPC, castration-resistant prostate cancer; SSE, symptomatic skeletal event.
Slide credit: clinicaloptions.com
Sartor O, et al. ASCO Abstract 5074.

4. Radium-223 Retreatment in CRPC: Eligibility Criteria
CRPC and bone metastases
Completion of 6 initial radium-223 injections with:
No bone progression during initial treatment
Radiographic or clinical progression after initial treatment
Adequate hematologic function
Pts ineligible if grade 3/4 AEs during or after initial radium treatment that did not resolve or led to discontinuation
Concomitant chemotherapy or initiation of abiraterone or enzalutamide treatment not permitted
Other agents allowed based on investigator discretion
AE, adverse event; CRPC, castration-resistant prostate cancer.
Slide credit: clinicaloptions.com
Sartor O, et al. ASCO Abstract 5074.

5. Radium-223 Retreatment in CRPC: Baseline Characteristics
Retreatment Study (N = 44)
ALSYMPCA (N = 614)
Median age, yrs (range)
71 (52-91)
71 (49-90)
ECOG PS 0/1/≥ 2, %
32/61/7
27/60/13
< 6/6-20/> 20 bone metastases, %
41/34/25
16/43/41
Prior treatment, %
Docetaxel
Abiraterone
Enzalutamide
Bisphosphonates
Denosumab 45 61 30 11 48 57 NA 20
Concurrent treatment, % 27 9 16
Median PSA, μg/L 68
146
CRPC, castration-resistant prostate cancer; ECOG, Eastern Cooperative Oncology Group; NA, not applicable; PS, performance status; PSA, prostate-specific antigen.
Slide credit: clinicaloptions.com
Sartor O, et al. ASCO Abstract 5074.

6. Radium-223 Retreatment in CRPC: Treatment Experience
Of the 44 pts who received retreatment:
All had received ≥ 2 prior hormonal regimens
45% had received ≥ 1 prior chemotherapy regimen
73% had failed novel hormonal agents (abiraterone, enzalutamide)
66% completed retreatment with all 6 injections
Median time from end of initial regimen to retreatment: 6 mos (range: mos)
CRPC, castration-resistant prostate cancer.
Slide credit: clinicaloptions.com
Sartor O, et al. ASCO Abstract 5074.

7. Radium-223 Retreatment in CRPC: Safety
TEAEs, %
Retreatment Study (N = 44)
ALSYMPCA (N = 600)
All Grades
Grade 3
Grade 4
Pts with ≥ 1 TEAE 93 41 7 35 9
Hematologic
Anemia
Thrombocytopenia
Leukopenia
Neutropenia 14 2 5 31 12 4 11 3 1
< 1
Nonhematologic (in > 10% of retreatment pts)
Fatigue
Nausea
Diarrhea
Decreased appetite
Arthralgia
Hypertension
Back pain
Fall
Vomiting 27 25 21 18 26 36 6 19
CRPC, castration-resistant prostate cancer; TEAE, treatment-emergent adverse event.
Slide credit: clinicaloptions.com
Sartor O, et al. ASCO Abstract 5074.

8. Radium-223 Retreatment in CRPC: Efficacy
Median time to several endpoints not yet reached: radiographic bone progression, OS, time to first SSE, SSE-FS, time to pain progression
5 pts (11%) died through 15.5-mo max OS follow-up
8 pts (14%) experienced first SSE through 14.1-mo max SSE, SSE-free survival follow-up
5 of 36 evaluable pts (14%) had pain progression through 7.3-mo max pain progression follow-up
Wk 24 pain progression event rate: 20%
CRPC, castration-resistant prostate cancer; SSE, symptomatic skeletal event.
Slide credit: clinicaloptions.com
Sartor O, et al. ASCO Abstract 5074.

9. Radium-223 Retreatment in CRPC: rPFS
Median rPFS: 9.9 mos
13 pts had rPFS events, largely consisting of soft tissue tumor progression (n = 8)
Only 1 pt with confirmed radiographic bone progression
12.8-mos max follow- up time for rPFS and radiographic bone progression
Radiographic PFS
100 80 60
rPFS (%) 40 20 2 4 6 8 10 12 14
CRPC, castration-resistant prostate cancer; rPFS, radiographic PFS.
Mos
Patients at risk 44 36 29 20 14 3 1
Slide credit: clinicaloptions.com
Sartor O, et al. ASCO Abstract 5074.

10. Radium-223 Retreatment CRCP: Conclusions
Second round of radium-223 treatment following initial course safe and feasible[1]
Well tolerated, with minimal hematologic toxicity
Low rate of radiographic bone progression
Encouraging early effects on OS, time to SSE, pain
Investigators conclude positive data warrant analysis of radium-223 retreatment in larger prospective trials[1]
Ongoing study to address expanded radium-223 dosing and duration of treatment[2]
CRPC, castration-resistant prostate cancer; SSE, symptomatic skeletal event.
1. Sartor O, et al. ASCO Abstract ClinicalTrials.gov. NCT
Slide credit: clinicaloptions.com

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