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La innovación como garantía de calidad asistencial: Cáncer de próstata Javier Puente, MD, PhD Hospital Universitario Clinico San Carlos Medical Oncology Department Complutense University Associate Professor of Medicine Innovación en Cáncer de Próstata Introduction - Since the approval of docetaxel we have learned much about the biology of prostate cancer - Multiple new drugs have demostrated safety and efficacy leading to aproval Treament algorithm Where We Are Now: Positive Phase 3 Trials in Met CRPC Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona Papel de docetaxel en CPHSM1 Papel de docetaxel en CP localizado de alto riesgo Nuevas entidades AP en el cáncer de próstata Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona Papel de docetaxel en CPHSM1 Papel de docetaxel en CP localizado de alto riesgo Nuevas entidades AP en el cáncer de próstata CPRCm Unfit - ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso Radium-223 ¿Abi/Enza? Fit Paciente asintomático o mínimamente sintomático ECOG 0-1 Tto. Hormonal Paciente con metástasis hepáticas y/o viscerales Quimioterapia Pacientes sintomáticos o con deterioro general por el tumor Abiraterone in Metastatic prostate cancer without previous chemotherapy R A N D O M I Z E D Patient Population Progressive mCRPC without prior chemotherapy; Asymptomatic or mildly symptomatic Co-primary end points: Abiraterone 1000 mg daily + Prednisone 5 mg BID (actual n = 546) aStratification by • OS Secondary end points: • Time to opiate use • Time to initiation of chemotherapy • Time to ECOG PS deterioration • Time to PSA progression Placebo daily + Prednisone 5 mg BID (actual n = 542) 1:1a • rPFS (central review) ECOG PS 0 vs 1. IA3 Unblinding FPI 2008 2009 LPI 2010 IA1 IA2 2011 FA 2012 2013 2014 OS with Abiraterone in mCRPC: median follow-up of 49.2 months Treatment effect more pronounced when adjusting for 44% of prednisone patients who received subsequent abiraterone (HR = 0.74) Third interim analysis data of rPFS Abiraterone in mCRPC (COU-302): secondary endpoints Abiraterone in mCRPC (COU-302): safety PREVAIL: A phase 3 trial of enzalutamide after progression on ADT in men with mCRPC Patient population: •1717 men with progressive mCRPC •Asymptomatic/ mildly symptomatic •Chemotherapy-naïve •Steroids allowed but not required R A N D O M I Z E D 1:1 Enzalutamide 160 mg/day (capsules) n=872 Co-primary endpoints: • OS • rPFS Placebo n=845 Enzalutamide reduced risk of death by 29% Enzalutamide Reduced Risk of Death by 29% Enzalutamide prolonged radiographic PFS Enzalutamide Prolonged Radiographic <br />Progression-Free Survival Secondary endpoints with Enzalutamide in the PREVAIL trial Most common Adverse Events <br />Most Common Adverse Events*<br /> CPRCm Unfit - ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso Radium-223 ¿Abi/Enza? Fit Paciente asintomático o mínimamente sintomático ECOG 0-1 ABiRATERONA VS ENZALUTAMIDA Paciente con metástasis hepáticas y/o viscerales Quimioterapia Pacientes sintomáticos o con deterioro general por el tumor Outcomes are evaluated by changes in disease manifestations PRESENT or which MAY OCCUR in the future Scher et al. Urology 2000 CPRCM0 CPRCm Unfit Fit - ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso Paciente asintomático o mínimamente sintomático ECOG 0-1 PSADT corto Gleason 8-10 LDH ↑ FA ↑ Resp. HT corto Radium-223 ¿Abi/Enza? ABiRATERONA VS ENZALUTAMIDA Paciente con metástasis hepáticas y/o viscerales ECOG 0 Oligometast Nodular pulmonar? Quimioterapia Pacientes sintomáticos o con deterioro general por el tumor Where are we going from here? Where are we going from here? Crawford ED, et al.ASCO 2014 CPRCM0 CPRCm Unfit Fit - ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso Paciente asintomático o mínimamente sintomático ECOG 0-1 PSADT corto Gleason 8-10 LDH ↑ FA ↑ Resp. HT corto Radium-223 ¿Abi/Enza? CPHSm1 ABiRATERONA VS ENZALUTAMIDA Paciente con metástasis hepáticas y/o viscerales ECOG 0 Oligometast Nodular pulmonar? Quimioterapia Pacientes sintomáticos o con deterioro general por el tumor Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona Papel de docetaxel en CPHSM1 Papel de docetaxel en CP localizado de alto riesgo Nuevas entidades AP en el cáncer de próstata The natural history of metastatic, hormone-naïve prostate cancer Abiraterone, Enzalutamide, Docetaxel, Cabazitaxel, Radium-223, Denosumab ADT M1 HSPC M1 HSPC UNDER CONTROL CRPC Time (Median 4-5 years) THE END The natural history of metastatic, hormone-naïve prostate cancer Hypothesis of CHAARTED and GETUG 15 phase III trials: - Early docetaxel will postpone progression to CRPC - Early docetaxel will postpone death M1 HSPC M1 HSPC UNDER CONTROL Time to progression Time to death CRPC THE END M1 HSMPC: 2 scenarios Docetaxel in HSPC: CLINICAL PFS IS IMPROVED Docetaxel in HSPC: Overall Survival Patient characteristics CHAARTED ADT + Doc (N=397) ADT alone (N=393) N % N % Low 134 33.8% 142 36.1% High 263 66.2% 251 63.9% 4-6 21 5.9% 21 6.1% 7 96 26.9% 82 23.9% 8-10 240 67.2% 240 70.0% Volume of Mets Gleason Score Unknown 40 PSA (ng/mL) at time of ADT start 50 Median 56.0 50.5 Range 0.4-8540.1 0.1-8056.0 OS by extend of metastatic disease at start of ADT Baseline Characteristics in GETUG-15 Slide 12 Presented By Gwenaelle Gravis at 2015 ASCO GU Key differences GETUG – E3805 •Case-Mix/Patient Characteristics • Lower burden of disease • Overall patients in GETUG15 on ADT alone had longer OS than E3805 •Access to more lines of therapy once CRPC • More non-LHRH therapy in E3805 •Sample size • GETUG15 half the sample size; less power •More non-PrCa and Rx related deaths: • Dilute the cancer control benefits (longer time to CRPC ADT+doc in GETUG15) • Greater dilution of potential OS benefit from decrease prostate cancer deaths if increase competing risks from other deaths if longer OS on ADT alone Slide 1 Presented By Nicholas James at 2015 ASCO Annual Meeting Inclusion criteria Presented By Nicholas James at 2015 ASCO Annual Meeting Outcome measures Presented By Nicholas James at 2015 ASCO Annual Meeting Docetaxel & ZA comparisons: patients Presented By Nicholas James at 2015 ASCO Annual Meeting Accrual Presented By Nicholas James at 2015 ASCO Annual Meeting Zoledronic acid: Failure-free survival Presented By Nicholas James at 2015 ASCO Annual Meeting Zoledronic acid: Survival Presented By Nicholas James at 2015 ASCO Annual Meeting Docetaxel: Failure-free survival Presented By Nicholas James at 2015 ASCO Annual Meeting Docetaxel: Survival Presented By Nicholas James at 2015 ASCO Annual Meeting Zoledronic acid + docetaxel: Failure-free survival Presented By Nicholas James at 2015 ASCO Annual Meeting Zoledronic acid + docetaxel: Survival Presented By Nicholas James at 2015 ASCO Annual Meeting Docetaxel: Survival – M1 Patients Presented By Nicholas James at 2015 ASCO Annual Meeting CPRCM0 CPRCm Unfit CPLocal Fit - ECOG ≥2 - Mala reserva medular: (pl < 100000, n: < 1000) - Neuropatía G2 - Comórbido, añoso Paciente asintomático o mínimamente sintomático ECOG 0-1 PSADT corto Gleason 8-10 LDH ↑ FA ↑ Resp. HT corto Radium-223 ¿Abi/Enza? CPHSm1 ABiRATERONA VS ENZALUTAMIDA Paciente con metástasis hepáticas y/o viscerales ECOG 0 Oligometast Nodular pulmonar? Quimioterapia Pacientes sintomáticos o con deterioro general por el tumor Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona Papel de docetaxel en CPHSM1 Papel de docetaxel en CP localizado de alto riesgo Nuevas entidades AP en el cáncer de próstata Docetaxel for localized, high-risk prostate cancer (RTOG 0521) Slide 3 Presented By Howard Sandler at 2015 ASCO Annual Meeting Docetaxel for localized, high-risk prostate cancer (RTOG 0521) Slide 4 Presented By Howard Sandler at 2015 ASCO Annual Meeting Docetaxel for localized, high-risk prostate cancer (RTOG 0521): DFS Slide 14 Presented By Howard Sandler at 2015 ASCO Annual Meeting Docetaxel for localized, high-risk prostate cancer (RTOG 0521): OS Slide 12 Presented By Howard Sandler at 2015 ASCO Annual Meeting OVERAL SURVIVAL Where are we going from here? • Additional uses for approved drugs • Additional (generally earlier) settings • Combinations • New versions of similar drugs • Treatment optimization • Mechanisms of resistance • Sequencing, combinations, biomarkers • New targets/drugs • New disease classifications • Precision medicine Innovación en Cáncer de Próstata Nuevos datos en CPRCM1 con Enzalutamida y Abiraterona Papel de docetaxel en CPHSM1 Papel de docetaxel en CP localizado de alto riesgo Nuevas entidades AP en el cáncer de próstata Dream Team Biopsy Trial Dream Team Biopsy Trial Presented By Eric Small at 2015 ASCO Annual Meeting Dream Team Biopsy Trial: histology of 124 evaluable biospies Histology of 124 Evaluable Biopsies<br />74 % were “pure” with a single histologic subtype (**isolated by LCM)<br />Remainder (26%) were comprised of mixed populations Presented By Eric Small at 2015 ASCO Annual Meeting Dream Team Biopsy Trial: IAC Slide 15 Presented By Eric Small at 2015 ASCO Annual Meeting Dream Team Biopsy Trial: histology of 124 evaluable biospies IAC and SCNC are equally distributed across all tissue types Presented By Eric Small at 2015 ASCO Annual Meeting Dream Team Biopsy Trial: histology of 124 evaluable biospies Overall survival as function of biopsy pathology<br />Grouping IAC and SCNC Presented By Eric Small at 2015 ASCO Annual Meeting THANK YOU Javier Puente, MD, PhD Hospital Universitario Clinico San Carlos Medical Oncology Department Complutense University Associate Professor of Medicine
