The Current Role of VEGF inhibition in the Management of Renal Cell Carcinoma

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The Current Role of VEGF inhibition in the
Management of Renal Cell Carcinoma
Dr. Paul Nathan Consultant Medical
Oncologist Mount Vernon Cancer Centre BUG
23-24th Sept 2005
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Fig 2. von Hippel-Lindau (VHL) gene product
normal and aberrant function
Rini, B. I. et al. J Clin Oncol 231028-1043 2005
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Fig 1. Vascular endothelial growth factor (VEGF)
receptor binding and intracellular signaling
Rini, B. I. et al. J Clin Oncol 231028-1043 2005
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Fig 3. Mechanism of activity of vascular
endothelial growth factor (VEGF) -directed agents
in renal cell carcinoma
Rini, B. I. et al. J Clin Oncol 231028-1043 2005
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A Randomized Trial of Bevacizumab, an
AntiVascular Endothelial Growth Factor Antibody,
for Metastatic Renal Cancer
James C. Yang, M.D., Leah Haworth, B.S.N.,
Richard M. Sherry, M.D., Patrick Hwu, M.D.,
Douglas J. Schwartzentruber, M.D., Suzanne L.
Topalian, M.D., Seth M. Steinberg, Ph.D., Helen
X. Chen, M.D., and Steven A. Rosenberg, M.D., Ph.D
NEJM 349, (5) 427-434 2003
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Rini, B. I. et al. J Clin Oncol 231028-1043 2005
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Current Open Studies of VEGF Inhibitors in Renal
cell Carcinoma
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SORCE A Phase III Randomised, Double Blind
Controlled Study Comparing SOrafenib With Placebo
In Patients With Resected Primary Renal CEll
Carcinoma At High or Intermediate Risk of Relapse
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• Patients with high and intermediate risk
• resected renal cell carcinoma

RANDOMISATION
Sorafenib 3 years
Placebo 3 years
Sorafenib 1 year Placebo 2 Years
Control arm 3 years of placebo (400mg po
bd) Experimental arm 1 1 year sorafenib 2
years placebo ( both 400mg po bd) Experimental
arm 2 3 years sorafenib (400mg po bd)
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Eligibility

• No evidence of residual disease after resection
  of RCC
• Leibovich prognostic score 3-8
• (high or intermediate risk of metastatic RCC or
  death)
• No prior anti-cancer treatment other than
  nephrectomy
• At least 4 weeks and no more than 4 months since
  surgery
• Subjects may be of any age without any other
  medical condition expected to reduce their life
  expectancy below 10 years from the time of trial
  entry
• Adequate bone marrow, renal and hepatic function
• Amylase lt1.5 x upper limit of normal
• Written informed consent before trial entry

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Timelines

• Feb 05 CTAAC Outline Approval
• May 05 Agreement on Revised Design
• Confirmed support of Bayer / Onyx
• June 05 Trial Development Group Formed
• Aug 05 Submission of Full CTAAC / TRICC
  Application
• October 05 CTAAC TRICC Approval
• Autumn 06 First Patient Recruited
• 2014 Analysis