Transcript www.OncologyEducation.ca TOXICITY

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
www.OncologyEducation.ca
Thank you for downloading this update. Please
feel free to use it for educational purposes.
Please acknowledge OncologyEducation.ca and
Dr. Lori Wood when using these slides.
www.OncologyEducation.ca
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
www.OncologyEducation.ca
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
www.OncologyEducation.ca
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%
www.OncologyEducation.ca
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
www.OncologyEducation.ca
RESULTS
Best Overall Effect on Bone Scan (n = 108)
•
•
•
•
CR = 19%
PR = 56%
SD = 21%
PD = 3%
www.OncologyEducation.ca
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)
www.OncologyEducation.ca
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.
www.OncologyEducation.ca
BOTTOM-LINE FOR CANADIAN
MEDICAL ONCOLOGISTS
• Very exciting drug
• Would be great to participate in clinical
trials with this drug
www.OncologyEducation.ca