authors: stadler wm et al, asco 2009. reviewed by: dr. lori wood abstract: 5017
DESCRIPTION
Randomized Trial of p53 Targeted Adjuvant Therapy for Patients (pts) With Organ-Confined Node-Negative Urothelial Bladder Cancer (UBC). Authors: Stadler WM et al, ASCO 2009. Reviewed by: Dr. Lori Wood Abstract: 5017 Date posted: June 12, 2009. Treatment A: Adjuvant MVAC x 3. R. - PowerPoint PPT PresentationTRANSCRIPT
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Randomized Trial of p53 Targeted Adjuvant Therapy for Patients (pts) With Organ-Confined Node-Negative
Urothelial Bladder Cancer (UBC)
Authors: Stadler WM et al, ASCO 2009.Reviewed by: Dr. Lori WoodAbstract: 5017Date posted: June 12, 2009
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RTreatment A:
Adjuvant MVAC x 3
Treatment B:
Observation
pT1-T2 N0M0 urothelialcancer, post cystectomy
and PLND
p53 positiven = 272 (p53 positive)n = 114 randomized
primary endpoint =time to recurrence
(goal: improvement by 20% at 3 years)
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STUDY RATIONALE
• Previous small studies showed that p53 positive tumors had probability of recurrence post resection in organ confined bladder cancer.
• Prior USC randomized trial of adjuvant chemotherapy versus observation showed improved outcome in p53 positive tumors.
• p53 positive cells may be more susceptible to chemotherapy agents that damage DNA.
• Hypothesis:
• p53 IHC is a valid biomarker
• p53 IHC is prognostic
• p53 IHC is predictive for benefit from DNA damaging chemotherapy
Cole et al, Nature 1997; 385:123
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RESULTS
• 521 patients registered
• 499 had successful p53 assessment
• 272 p53 positive ( 10% nuclear reactivity)
• 158 refused randomization
• 114 randomized (only 42% of p53 positive)
• 56 observation
• 46 MVAC
• 12 refused
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RESULTS (CONTINUED)
• n = 499; 5-year relapse-free survival = 80%.
• no difference if p53 positive or negative
• n = 114; 5-year relapse-free survival = 83%.
• no difference if MVAC or observation
• Therefore, p53 positivity was not of prognostic or predictive value.
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STUDY COMMENTARY
• Study was halted early by DSMB after review of futility analysis.
• Only 42% of p53 positive patients were randomized.
• Lower than expected event rate and failure (i.e.: 15% recurrence rate at 3 years) and the a priori hypothesis was 50%; therefore, study very underpowered.
• Lower event rate probably because only pT1-T2 N0 disease and excluded pT3-T4 or N+ disease.
• p53 positivity not predictive or prognostic.
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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS
• p53 as assessed by IHC will not help guide therapeutic decisions in resected bladder cancer at this point in time.
• The role of adjuvant chemotherapy in all stages of (pT1-T4 N0 or N+) resected bladder cancer is still very controversial and understudied.