Cabozantinib (XL184) in metastatic castrationresistant prostate cancer (mCRPC): Results from a
phase II randomized discontinuation trial.
Authors: Hussain M. et al, ASCO 2011
Abstract: 4516
Reviewed by: Dr. Lori Wood
Date posted: June 2011
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STUDY RATIONALE
• New agents for metastatic CRPCa are needed
• Cabozantinib (XL184)
– An oral TKI of MET and VEGFR
– MET drives tumor cell invasion and metastases
– MET and VEGFR synergize to promote angiogenesis
• In prostate cancer
– Pre-clinically – ADT  MET expression
– MET  with progression and metastases
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STUDY DESIGN
Phase III Randomized Discontinuation Trial
- Metastatic CRPCa patients:
- 0-1 prior chemotherapy
- all received Cabozantinib
100 mg p.o. qd x 12 weeks
- Primary objectives:
- lead-in stage – RECIST RR
- randomized stage - PFS
- Planned n=200; accrual
discontinued after n=171 due
to better than expected
results
PR/CR
SD
Continue
Continue (n=14)
R
Placebo (n=17)
PD
Stop
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RESULTS
At 12 Weeks
PR/CR
SD
Off Study
Open Label Extension
Randomized
n=61 (36%)
n=79 (46%)
n=31 (18%)
PD = 16%
AE = 15%
Death = 1%
Other = 4%
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RESULTS
• Lead-in stage
–
–
–
–
–
68% overall objective disease control at week 12
74% measurable soft tissue disease regression
76% complete or partial bone scan resolution
67% improvement in pain
PSA changes did not correlate with radiological
response
• Randomization stage
– PFS = 21 weeks vs. 6 weeks
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RESULTS
Best Overall Effect on Bone Scan (n = 108)
•
•
•
•
CR = 19%
PR = 56%
SD = 21%
PD = 3%
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TOXICITY
• Grade  3 adverse events in lead-in stage
–
–
–
–
–
–
Fatigue = 16%
Thrombosis = 7%
Hypertension = 6%
Hand/Foot = 6%
Anorexia = 5%
GI Perforation = 2%
• 51% of patients had  dose reduction
• 1 death potentially 2 treatment (unexplained
death)
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STUDY COMMENTARY
• Cabozantinib is a first in class TKI to act on both MET
and VEGFR.
• This phase II randomized discontinuation study with
Cabozantinib showed very impressive results, especially
bone scan and pain improvement.
• Will the endpoints looked at (bone scan and pain
improvement) translate into an improvement in overall
survival?
• This drug is in many other clinical trials right now with
prostate cancer patients and no doubt we will hear a lot
more about it.
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BOTTOM-LINE FOR CANADIAN
MEDICAL ONCOLOGISTS
• Very exciting drug
• Would be great to participate in clinical
trials with this drug
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