Similaire à NY Prostate Cancer Conference - M.H. Hussain - Session 5: Predicting response to hormonal therapy and survival in men with metastatic disease
Similaire à NY Prostate Cancer Conference - M.H. Hussain - Session 5: Predicting response to hormonal therapy and survival in men with metastatic disease (20)
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NY Prostate Cancer Conference - M.H. Hussain - Session 5: Predicting response to hormonal therapy and survival in men with metastatic disease
1. Predicting Response to Hormonal Therapy and Survival in Men with Metastatic Prostate Cancer Maha Hussain, M.D., FACP Professor of Medicine & Urology Associate Director For Clinical Research Co-Leader, Prostate Cancer/GU Oncology Program University of Michigan Comprehensive Cancer Center
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3. PCa, prostate cancer; NR, not recorded; PFS, progression-free survival; MS, median survival; a Goserelin + flutamide arm superior in subjective and objective PFS, OS and rate of cancer deaths Selected Randomized Studies of Combined AD vs Monotherapy in M1 PCa Crawford ED et al. N Engl J Med 1989;321:419–24 Keuppens F et al. Cancer 1993;72(12 suppl):3863–9 Tyrrell C et al. Cancer 1993;72(12 suppl):3878–9 Eisenberger M et al. N Engl J Med 1998;339:1036–42 Author Treatment n PFS (months) OS (months) p Crawford, 1989 Leuprolide + placebo Leuprolide + flutamide 300 303 13.9 16.5 28.3 35.6 0.03 (PFS) 0.03 (OS) Keuppens, 1993 Orchidectomy Goserelin + flutamide a 163 161 Diff (subj) 8.1 Diff (obj) 11.0 Diff (ms) 7 Diff (c) 15 0.009 (PFS) 0.05 (OS) Tyrrell, 1993 Goserelin Goserelin + flutamide 282 287 NR NR 37.7 42.4 0.08 (PFS) 0.14 (OS) Eisenberger, 1998 Orchidectomy + placebo Orchidectomy + flutamide 687 700 18.6 20.4 29.9 33.5 0.26 (PFS) 0.16 (OS)
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7. Long Term Survival for S8894 Data as of 10/1/2008 Tangen et al, Clin Prostate Cancer, 2003
8. Clinical Predictors of Survival Multivariate Proportional Odds Model (n = 536) Tangen et al, Clin Prostate Cancer, 2003 Variable Estimated DR (95% CI) р Value Flutamide vs. Placebo 0.72 (0.47, 1.12) 0.14 Extensive vs. Minimal Disease 2.90 (1.78, 4.73) <0.0001 Performance Status (2/3 vs. 0/1) 1.22 (0.63,2.36) 0.56 Bone Pain (Yes vs. No) 2.61 (1.66, 4.12) <0.0001 Race (Black vs. Others) 1.19 (0.67, 2.10) 0.56 Gleason Score <7 1.0 (reference) - 7 1.84 (0.94, 3.60 0.076 >7 3.79 (2.00, 7.18) <0.0001 Log (PSA) 1.18 (1.03, 1.34) 0.016 Age 1.02 (1.00, 1.05) 0.082
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12. PSA (ng/mL) Patients (%) Q #1: Patients with Specified PSA Levels During or at the End of 7 Months ADT Induction (n=1395) Hussain M et al. J Clin Oncol 2006;24:3984–90
13. Multivariate Logistic Regression Model Predicting Lack of Achieving a PSA < 4.0 ng/ml During Induction Adjusted for Other Variables in the Model (n=1395) The results are similar for achieving PSA ≤ 4.0 ng/ml at any time during induction Significant (p<0.05) univariate predictors with < 15% missing are included in this model Lack of PSA ≤ 4.0 ng/ml at Months 6 &7 Predictor Odds Ratio (95% CI) P-value Age at Study Entry in 5 Year increments 0.93 (0.86, 1.00) 0.048 Prestudy PSA in 50 unit increments 1.02 (1.01, 1.03) <0.0001 Performance Status 2,3 vs. 0,1 1.88 (1.09, 3.25) 0.023 Gleason sum ≥ 8 1.97 (1.49, 2.60) <0.0001 Bone Pain Present 2.25 (1.70, 2.99) <0.0001
14. Q#2: Predictors of Risk of Death After 7 Months ADT, n=1,345 Predictor Univariate Hazard Ratio (95% CI) P-value Bone Pain Present 1.91 (1.63, 2.24) <.0001 Performance Status 2,3 vs. 0,1 1.83 (1.39, 2.41) <.0001 Gleason Sum 8 or higher 1.58 (1.34, 1.87) <.0001 Weight Change 1.57 (1.31, 1.88) <.0001 Positive Distant Nodes 1.34 (1.03, 1.73) 0.027 Prestudy PSA in 50 unit increments 1.01 (1.00, 1.01) 0.0024 Any PSA < 4ng/ml 0.26 (0.22, 0.31) <.0001 PSA < 4ng/ml at Months 6&7 0.20 (0.17, 0.23) <.0001 Any PSA < 0.2 ng/ml 0.34 (0.29, 0.40) <.0001 Any PSA < 0.2 ng/ml at Months 6&7 0.30 (0.26, 0.36) <.0001
15. Multivariate Proportional Hazards Model: Testing Effect of PSA < 4 ng/ml or < 0.2 at Months 6,7 on Subsequent Risk of Death (Estimates and p-values adjusted for other variables in the model) # comparison of these two estimates with a Wald chi-square, p <0.0001. Significant (p<0.05) univariate predictors with < 15% missing included in model Predictor Hazard Ratio (95% CI) P-value Performance Status 2 vs 0,1 1.86 (1.34, 2.60) <0.001 Bone Pain Present 1.50 (1.25, 1.80) <0.0001 Gleason sum ≥8 1.35 (1.13, 1.62) 0.001 Prestudy PSA in 50 unit increments 0.99 (0.99, 1.00) 0.005 0.2 < PSA < 4 ng/ml at Months 6 & 7 0.30 # (0.24, 0.38) <0.0001 PSA ≤ 0.2 ng/ml at Months 6&7 0.17 # (0.13, 0.21) <0.0001
16. At Risk PSA ≤ 0.2 ng/ml 453 210 63 0.2 < PSA ≤ 4.0 219 77 20 PSA > 4.0 92 17 7 Hussain et al. J Clin Oncol 2006;24:3984–90 Overall Survival by By PSA Status at End of 7 month ADT Induction 0% 20% 40% 60% 80% 100% 0 24 48 72 96 120 Months After End of Induction PSA ≤ 0.2 0.2 < PSA ≤ 4.0 PSA > 4.0 At Risk 602 360 383 Deaths 199 166 322 Median in Months 75 44 13 P < .0001
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18. PSA-P as a Predictor of Overall Survival (Time Varying Analysis, Multivariate Cox Regression)
19. Landmark Analysis S9346 Overall Survival by PSA-P at 7 Months (PCWG 08: ≥ 25% & ≥ 2 ng/mL ) 0% 20% 40% 60% 80% 100% 7 31 55 79 103 127 151 Months After Registration No PSA Progression PSA Progression N 829 200 Events 465 191 Median in months 44 (51) 10 (17) P<.0001
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22. PSA -Based Personalized Therapy 2. Induce a response in suboptimal PSA – Responders About 30% of all registered patients to S9346 had a PSA > 4 at 7 months BUT not rising S1014: Abiraterone acetate for patients not achieving a PSA 4 ng/mL after 7 months of CAD