Asymptomatic Metastatic Castrate Resistant Prostate Cancer Miki - - PowerPoint PPT Presentation

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Nov 18, 2022 451 likes •652 views

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

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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

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

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Should we treat Asymptomatic mCRPC?

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

Harm Benefit

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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

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Asymptomatic mCRPC

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

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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

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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

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IMPACT Trial: Survival Analysis

(Kantoff et al., 2010)

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

Sipuleucel-T

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

Sipuleucel-T

IMPACT Trial: Safety Analysis

(Kantoff et al., 2010)

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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

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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

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Sipuleucel-T

Meta-analysis – Safety Analysis

(Kawalec, Paszulewicz, Holko, & Pilc, 2012)

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

All A.E. Grade 3-5 CVA

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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

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Prevail Study: Survival Analysis

(Beer et al., 2017; Beer et al., 2014)

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

rPFS OS

Enzalutamide

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Enzalutamide

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

Prevail Study: Safety Analysis

(Beer et al., 2017; Beer et al., 2014)

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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

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

rPFS OS

Abiraterone

COU-AA-302 Study: Survival analysis

(Rathkopf et al., 2014; Ryan et al., 2013)

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Abiraterone

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

COU-AA-302 Study: Safety analysis

(Rathkopf et al., 2014; Ryan et al., 2013)

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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