NOVITÀ IN TEMA DI NEOPLASIA DELLA PROSTATA L ALGORITMO TERAPEUTICO NEL CARCINOMA DELLA PROSTATA METASTATICO SENSIBILE ALLA CASTRAZIONE
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1 NOVITÀ IN TEMA DI NEOPLASIA DELLA PROSTATA L ALGORITMO TERAPEUTICO NEL CARCINOMA DELLA PROSTATA METASTATICO SENSIBILE ALLA CASTRAZIONE S.S. Oncologia Medica Genitourinaria
2 Outline 1. Clinical case 2. Chemotherapy 3. Hormone therapy 4. Trials ongoing
3 Background Metastatic hormone-sensitive prostate cancer incidence is: - 3% in US and rising; - 6% across Europe % 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 Buzzoni C et al. Eur Urol Chen R et al. Asian J Urol Ito K et al. Nat Rev Urol Nardi AC et al. Int Braz J Urol Yamaoka M et al. Clin Cancer Res. 2010
4 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
5 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/ /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
6 Lung PR
7 From clinics to literature
8 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
9 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
10 High Volume Low Volume Gravis G. et al Eur Urol. Raffaele 2016 Ratta
11 High Volume de novo metastatic pts Low Volume de novo metastatic pts Gravis G. et al Eur Urol. Raffaele 2016 Ratta
12 High Volume pts with prior local therapy Low Volume pts with prior local therapy Gravis G. et al Eur Urol. Raffaele 2016 Ratta
13 James ND. et al. Lancet 2016
14 No stratification by extent of metastatic disease James ND. et al. Lancet 2016
15 James ND. et al. Lancet 2016
16
17 Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, James N et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017.
18 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
19 Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
20 Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
21 Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
22 Fizazi K et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
23 James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
24 James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
25 James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
26 James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
27 James ND et al. Presented at 2017 ASCO Annual Meeting. Chicago, IL, USA: June 2-6, 2017, NEJM 2017
28 What is better for hormone-sensitive patients starting ADT? Doc or Abi???
29 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.
30 ABI DOC
31 This is not a true randomized trial (only a part) Sydes M et al ESMO Annual Meeting
32 Trials ongoing Sartor O, NEJM 2018
33 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
34 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
35 The results of LATITUDE and STAMPEDE trials will change our clinical practice? Not yet.soon!
36 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
37 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
38 Grazie per l attenzione raffaele.ratta@istitutotumori.mi.it
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