Asymptomatic Metastatic Castrate Resistant Prostate Cancer Miki - PowerPoint PPT Presentation

Asymptomatic Metastatic Castrate Resistant Prostate Cancer Miki Haifler, MD, M.Sc Urologic Oncology Department of Urology Shamir (Assaf Haroffeh) Medical Center Sackler Faculty of Medicine Tel-Aviv University

To Treat or Not to Treat? “And what’s he then that says I play the villain?” William Shakespeare, Othello

Should we treat Asymptomatic mCRPC? Benefit Harm Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Asymptomatic mCRPC Index Patient • Rising PSA • Castrate levels of testosterone • Documented metastatic disease on imaging • Chemotherapy naïve • Asymptomatic and opiate free Miki Haifler, MD, M.Sc, , Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Asymptomatic mCRPC Miki Haifler, MD, M.Sc, , Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Outline Discuss available level 1 evidence for: • Sipileucel-T • Enzalutamide • Abiraterone Miki Haifler, MD, M.Sc, , Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Sipuleucel-T IMPACT Trial (Kantoff et al., 2010) – 512 Asymptomatic mCRPC patients • 341 pts in intervention arm • 171 pts in control arm – Median FU 34.1 months – HR for death: 0.78 (95%CI 0.61-0.98) – Median survival: 25.8 vs 21.7 months Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Sipuleucel-T IMPACT Trial: Survival Analysis (Kantoff et al., 2010) Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Sipuleucel-T IMPACT Trial: Safety Analysis (Kantoff et al., 2010) Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Sipuleucel-T Meta-analysis (Kawalec, Paszulewicz, Holko, & Pilc, 2012) – 3 Phase III RCTs (D9901, D9902A, IMPACT) – 737 pts • 488 intervention arm • 249 control arm Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Sipuleucel-T Meta-analysis – Survival Analysis (Kawalec, Paszulewicz, Holko, & Pilc, 2012) Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Sipuleucel-T Meta-analysis – Safety Analysis (Kawalec, Paszulewicz, Holko, & Pilc, 2012) CVA Grade 3-5 All A.E. Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Enzalutamide Prevail Study (Beer et al., 2017; Beer et al., 2014) – 1717 Asymptomatic mCRPC patients • 872 pts in intervention arm • 845 pts in control arm – Median FU 31 months (Interim analysis) – HR for death: 0.77 (95%CI 0.67-0.88) – Median survival: 35.3 vs 31.3 months – HR for progression or death: 0.32 (95%CI 0.28-0.37) Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Enzalutamide Prevail Study: Survival Analysis (Beer et al., 2017; Beer et al., 2014) OS rPFS Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Enzalutamide Prevail Study: Safety Analysis (Beer et al., 2017; Beer et al., 2014) Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Abiraterone COU - AA-302 Study (Rathkopf et al., 2014; Ryan et al., 2013) – 1088 Asymptomatic mCRPC patients • 546 pts in intervention arm • 542 pts in control arm – Median FU 27.1 months (Interim analysis 3) – HR for death: 0.79 (p=0.0151) – Median survival: 35.3 vs 30.1 months – HR for progression or death: 0.52 (p<0.0001) Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Abiraterone COU - AA-302 Study: Survival analysis (Rathkopf et al., 2014; Ryan et al., 2013) OS rPFS Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Abiraterone COU - AA-302 Study: Safety analysis (Rathkopf et al., 2014; Ryan et al., 2013) Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel

Conclusions – Selecting a treatment approach that will optimize patient outcomes is challenging – Large-scale, randomized, controlled clinical trials evaluating combination, sequential, and direct comparative protocols are needed Miki Haifler, MD, M.Sc, Department of Urology, Shamir (Assaf Harofeh) MC, Tzrifin, Israel