Surrogacy Case Study: Prostate Specific Antigen (PSA ... - Isped

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Explanation? • Time to testosterone recovery relates to duration of ADT and strongly influences the time to biochemical relapse Results obtained on trials with only short term ADT may not generalize to studies randomizing between longer durations of ADT Other comments (from Denham et al.): 1. PSADT strongly dependent on #PSA values available 2. Cut-point on PSA-DT or TTBF not clearly defined 3. Need a meta-analysis validation
PSA response or PSA-V surrogate for survival in HRPC? • Meta-analytic validation in 2 studies of liarozole versus CPA/FLU (1) • PSA response (50% decline) not a surrogate for OS • SWOG-9916: Docetaxel+Estramustine vs M+P (2) • PSA response (first 3 m) not a surrogate for OS • PSA velocity (first 3 m) is a surrogate for OS by Prentice criteria and should be further investigated • Tax 327: Docetaxel(D)(q1s)+Prednisone(P) vs D(q3s)+P vs Mitoxantrone(M)+P (3) • PSA response (50% decline from entry) not validated as surrogate for OS • Other changes in PSA or PSA kinetics are weaker surrogates 1. Buyse M. et al In Biomarkers in Clinical Drug Development. Springer-Verlag, 2003 2. Crawford et al. ASCO 2004, abs. 4505, Petrylak DP. J Natl Cancer Inst 2006. 3. Roessner M et al. ASCO 2005, abs. 391s.; Armstrong AJ et al. JCO 2007
Page 1 and 2: EORTC Surrogacy Case Study: Prostat
Page 3 and 4: Prostate Specific Antigen (PSA) •
Page 5 and 6: Transition between clinical states
Page 7 and 8: Surrogate endpoint • An outcome m
Page 9 and 10: Meta-analytic validation First stag
Page 11 and 12: PSA - defined endpoints in prostate
Page 13 and 14: PSA “surrogacy” studies in the
Page 15 and 16: Published PSA surrogacy studies Col
Page 17 and 18: Review • 2 meta-analytic validati
Page 19 and 20: PSA endpoints PSA normalization A P
Page 21 and 22: PSA data (M1) Mean log(PSA) -2 0 2
Page 23 and 24: Treatment effects on OS against tre
Page 25 and 26: Prediction for a new trial - M1 •
Page 27 and 28: PSA doubling-free survival (PSA-D)
Page 29 and 30: Recommendation, M1 hormone sensitiv
Page 31 and 32: 4m vs 24m ADT adjuvant to irradiati
Page 33: PSA-DT and TTBF surrogate for PCa-s
Page 37 and 38: Of interest… The search for the g
Page 39 and 40: Conclusions for HRPC on chemotherap
Page 41 and 42: ASCENT trial High dose Calcitriol (
Page 43 and 44: Be aware of your drug’s effect on

Surrogacy Case Study: Prostate Specific Antigen (PSA ... - Isped

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