the role of early hormonal manipulation and immunotherapy in crpc · 2018-07-17 · the role of...
TRANSCRIPT
![Page 1: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/1.jpg)
The role of early hormonal manipulation andimmunotherapy in CRPC
Orazio CaffoMedical Oncology Dept. Trento
![Page 2: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/2.jpg)
CSPC
CRPC
Enzalutamide
Cabazitaxel
Abiraterone
Abiraterone
Docetaxel
Enzalutamide
Ra 223
ADT
AntiAndrogens
Abiraterone
Docetaxel
The landscape before ASCO GU 2018
CSPC
CRPC
![Page 3: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/3.jpg)
CSPC
CRPC
Enzalutamide
Cabazitaxel
Abiraterone
Abiraterone
Docetaxel
Enzalutamide
Ra 223
ADT
AntiAndrogens
Abiraterone
Docetaxel
The landscape before ASCO GU 2018
CSPC
CRPC
CRPC
![Page 4: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/4.jpg)
CSPC
CRPC
Enzalutamide
Cabazitaxel
Abiraterone
Abiraterone
Docetaxel
Enzalutamide
Ra 223
ADT
AntiAndrogens
Abiraterone
Docetaxel
The landscape at ASCO GU 2018
Enzalutamide
Apalutamide
CSPC
CRPC
CRPC
![Page 5: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/5.jpg)
One specific concern in the clinical development of ENZ was theinduction of seizures in patients with a predisposition, which is thoughtto be secondary to binding of GABA-A receptors in CNS.With a lower efficacious dose (and subsequently lower levels of drugpresent in the CNS) a potential advantage of APA is reduced risk of seizures.
![Page 6: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/6.jpg)
![Page 7: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/7.jpg)
![Page 8: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/8.jpg)
SPARTAN PROSPER
MFS (exp arm) 40.5 mos 36.6 mos
HR 0.28 0.29
MFS improvement 24.3 mos 21.9 mos
![Page 9: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/9.jpg)
![Page 10: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/10.jpg)
![Page 11: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/11.jpg)
![Page 12: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/12.jpg)
![Page 13: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/13.jpg)
![Page 14: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/14.jpg)
![Page 15: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/15.jpg)
![Page 16: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/16.jpg)
Open questions
• Is MFS an appropriate endpoint?
![Page 17: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/17.jpg)
Open questions• Is PSA a reliable predictor of disease progression
during APA/ENZ treatment?
• Does the impact on PSA suggest that these agents may alter the biology of nmCRPC?
![Page 18: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/18.jpg)
Open questions
• Should the toxicity profile temper the enthusiastic feelings about the disease control improvement?
• Could confidence in these agents be greater if understanding of the side effects will be better?
![Page 19: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/19.jpg)
Open questions
• The trials used conventional imaging approach, with CT scans and bone scans: could more recent imaging techniques (fluciclovine PET, PSMA PET) potentially able to earlier detect metastases, shrink the population of men with nmCRPC?
![Page 20: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/20.jpg)
CSPC
CRPC
Enzalutamide
Cabazitaxel
Abiraterone
Abiraterone
Docetaxel
Enzalutamide
Ra 223
ADT
AntiAndrogens
Abiraterone
Docetaxel
The landscape at ASCO GU 2018
Enzalutamide
Apalutamide
CSPC
CRPC
CRPC
NEW TARGETS
Homologous recombination gene deficiencyImmune check-point
![Page 21: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/21.jpg)
• 692 pts
• 82 (11.8%) at least one presumed pathogenic germline mutation in a gene involved in DNA-repair processes
• 16 different genes [BRCA2 (37 mutations)]
![Page 22: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/22.jpg)
Robinson Cell 2015
![Page 23: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/23.jpg)
![Page 24: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/24.jpg)
![Page 25: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/25.jpg)
![Page 26: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/26.jpg)
![Page 27: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/27.jpg)
![Page 28: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/28.jpg)
![Page 29: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/29.jpg)
![Page 30: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/30.jpg)
![Page 31: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/31.jpg)
![Page 32: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/32.jpg)
![Page 33: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/33.jpg)
![Page 34: The role of early hormonal manipulation and immunotherapy in CRPC · 2018-07-17 · The role of early hormonal manipulation and immunotherapy in CRPC Orazio Caffo Medical Oncology](https://reader033.vdocuments.site/reader033/viewer/2022053008/5f0c0a2a7e708231d4337356/html5/thumbnails/34.jpg)
Conclusions
• Practice-changing news concerned the nmCSPCsetting
• Exciting perspectives are related to growingevidences about the activity of PARPi and iCKi