NOVITÀ IN TEMA DI NEOPLASIA DELLA PROSTATA L ALGORITMO TERAPEUTICO NEL CARCINOMA DELLA PROSTATA METASTATICO SENSIBILE ALLA CASTRAZIONE S.S. Oncologia Medica Genitourinaria
Outline 1. Clinical case 2. Chemotherapy 3. Hormone therapy 4. Trials ongoing
Background Metastatic hormone-sensitive prostate cancer incidence is: - 3% in US and rising; - 6% across Europe - 4-10% in Latin America - 60% in Asia-Pacific Historically, androgen deprivation therapy (ADT) has been the standard of care Most men with metastases progress to mcrpc largely driven by reactivation of AR signaling Weiner AG et al. Prostate Cancer Prostatic Dis. 2016 Buzzoni C et al. Eur Urol. 2015 Chen R et al. Asian J Urol. 2014 Ito K et al. Nat Rev Urol. 2014 Nardi AC et al. Int Braz J Urol. 2012 Yamaoka M et al. Clin Cancer Res. 2010
Let s start from clinics! 68 yo man Comorbidities: Type II Diabetes Mellitus Obesity May 2017: PSA 129 ng/ml 14/06/17 Bone scan: negative 19/06/17 Prostatic biopsy: adenocarcinoma, Gleason Score 4+4=8 11/07/17 CT scan (T/A): multiple lung secondary lesions
07/2017 Start LHRHa q 28 + bicalutamide 50 mg/die (for 1 month) 26/09/2017 PSA 8 ng/ml (vs 129) Main characteristics of my patient: Newly diagnosed metastatic prostate cancer Gleason score 8 Lung secondary lesions 09/10/2017-22/01/2018 Docetaxel 75 mg/mq q21 + prednisone 5 mg bid (6 cycles) 04/12/2017 PSA 1.4 ng/ml 09/02/2018 PSA 1.35 ng/ml 12/03/2018 CT scan
Lung PR
From clinics to literature
Low Volume GETUG-AFU 15: biochemical PFS and rpfs for ADT+docetaxel but no significant OS benefit Subsequent retrospective analysis: High Volume Gravis G. et al Eur Urol. 2016
HIGH VOLUME: presence of visceral metastases or 4 bone lesions with 1 beyond the vertebral bodies and pelvis Gravis G. et al Eur Urol. Raffaele 2016 Ratta
High Volume Low Volume Gravis G. et al Eur Urol. Raffaele 2016 Ratta
High Volume de novo metastatic pts Low Volume de novo metastatic pts Gravis G. et al Eur Urol. Raffaele 2016 Ratta
High Volume pts with prior local therapy Low Volume pts with prior local therapy Gravis G. et al Eur Urol. Raffaele 2016 Ratta
James ND. et al. Lancet 2016
No stratification by extent of metastatic disease James ND. et al. Lancet 2016
James ND. et al. Lancet 2016
Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017. James N et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017.
High-risk defined as meeting at least 2 of 3 high-risk criteria: Gleason score of 8 Presence of 3 lesions on bone scan Presence of measurable visceral lesion Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
What is better for hormone-sensitive patients starting ADT? Doc or Abi???
Comparing Overall Survival Across Studies Overlay of LATITUDE KM Plot on CHAARTED (High Volume) KM Plot *Estimated from KM plots Small E. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017.
ABI DOC
This is not a true randomized trial (only a part) Sydes M et al. 2017 ESMO Annual Meeting
Trials ongoing Sartor O, NEJM 2018
Let s summarize Main characteristics of my patient: Newly diagnosed metastatic prostate cancer Gleason score 8 Lung secondary lesions LATITUDE trial: High-risk defined as meeting at least 2 of 3 high-risk criteria: Gleason score of 8 Presence of 3 lesions on bone scan Presence of measurable visceral lesion CHARTEED trial: High-volume disease defined as: presence of visceral metastases or 4 bone lesions with 1 beyond the vertebral bodies and pelvis
Disease burden (high volume vs low volume) Disease risk (high vs low) Long term steroids? Toxicity profiles Patient s characteristics (age, comorbidities) Symptoms Cost-effectiveness Availability Patient s preference
The results of LATITUDE and STAMPEDE trials will change our clinical practice? Not yet.soon!
Take home messages Docetaxel and Abiraterone improve survival in hormone-sensitive newly diagnosed patients with metastatic high volume disease Docetaxel should be considered for routine practice in suitable men with newly-diagnosed high volume metastatic disease Patients selection will be fundamental Treatments should be tailored on patients characteristics
Take home messages Docetaxel and Abiraterone improve survival in hormone naïve newly diagnosed patients with metastatic high volume disease Docetaxel should be considered for routine practice in suitable men with newly-diagnosed high volume metastatic disease Patients selection is fundamental Treatments should be tailored on patients characteristics
Grazie per l attenzione raffaele.ratta@istitutotumori.mi.it