Metastatic castration sensitive prostate cancer (mCSPC) Silke Gillessen, MD Medical Oncology Division of Cancer Sciences , University of Manchester and The Christie, Manchester, UK and Kantonsspital St.Gallen, Switzerland Switzerland [email protected]
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Metastatic castration sensitive prostate cancer (mCSPC) · Metastatic castration sensitive prostate cancer (mCSPC) Silke Gillessen, MD Medical Oncology Division of Cancer Sciences
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Metastatic castration sensitive prostate cancer (mCSPC)
Silke Gillessen, MDMedical Oncology
Division of Cancer Sciences , University of Manchester and The Christie, Manchester, UKand
Abiraterone acetate 1000mg OD until PDPrednisone 5mg OD
ADT
Castration-sensitive/naïve men
LATITUDE
only «high-risk» M1 at least 2/3 Criteria
• Gleason score ≥8
• ≥3 Bone metastases
• Visceral metastases
STAMPEDE
LATITUDE: ADT vs ADT + Abiraterone/Pred
Fizazi NEJM 2017
«High-risk» Criteria:
• Gleason score ≥8 + ≥3 bone lesions ca. 95%
• Gleason score ≥8 + visceral disease ca. 14%
• ≥3 bone lesions + visceral disease ca. 14%
• Gleason score ≥8 + ≥3 bone lesions + ca. 12%
• visceral disease
Median age: ca. 68 years
LATITUDE only «high-risk» M1 at least 2/3 Criteria
• Gleason score ≥8
• ≥3 Bone metastases
• Visceral metastases
Fizazi K et al, New Engl J Med 2017
AEs of Abi/Pred given at start of ADT (mCSPC)
STAMPEDE Trial – MAMS design
+ ?
Practise changing!
ESMO 2018!Practise changing!
STAMPEDE: ADT vs ADT + Abiraterone/Pred
Metastatic:
- Newly diagnosed M1 ca. 50%
- M1 after local therapy ca. 4%
Non-metastatic
- De novo N+ ca. 20%
- Newly diagnosed node negative ca. 27%
- Biochemical recurrence ca. 2%
Median age: 67 years
James N et al, New Engl J Med 2017
ADT + Abiraterone/Pred: Metaanalysis
Effect of adding AAP to ADT on (A) overall survival and (clinical/radiological) progression-free survival (B) in
M1 CNPC
Rydzewska et al Eur J Cancer 2017
ESMO NCCN EAU
Docetaxel ADT plus docetaxel is recommended as first-line treatment of metastatic, hormone-naïve disease in men fit enough forchemotherapy
For M1: ADT + Docetaxel (patients with low-volume disease have less certain benefit from early docetaxel).
In newly diagnosed M1 patients, offer castration combined with docetaxel, provided patients are fit enough to receive chemotherapy.
Abiraterone ADT plusabiraterone/prednisonemay be considered as first-line treatment formetastatic, hormone-naive disease
For M1: ADT +Abiraterone Offer castration combined with abiraterone acetate plus prednisone to all patients whose first presentation is M1 disease and who are fit enough for the regimen
Guidelines
Sydes M et al ESMO 2017, Ann Oncol 2018
Comparison Abi/P and Docetaxel
STAMPEDE patientsIncluded in arm SOC + Docetaxel (n=189)or arm SOC + Abiraterone/P (n=377)between Nov 2011 and Mar 2013
Comparison not planned and poweredin the usual way!
No evidence of a difference on overall orprostate cancer-specific survival
AAP has highest probabilityof being the most effective, but uncertainty remains…
Sternberg ESMO 2017
Castration-sensitive/naïve prostate cancer:Very rapidly changing space
Ongoing randomized de novo mCSPC trials: role of local therapy
Control Arm Experimental Arm Acronyms Sponsor
SOC ADT +/- Abi
SOC + Prostate RTADT +/- Prostate RT +/- Abi +/-Docetaxel
STAMPEDE Arm HPEACE 1
MRC: ESMO 2018Unicancer
Best systemic therapy BST + RP or RT MDACC(Fox Chase/UCSF)
ADT ADT + Prostate RT HORRAD Netherlands*
Best systemic Rx BST+ local therapy(some limited to oligometsonly)
TROMBONEg-RAMPP
UKMartini-Klinik
* Boeve et al Eur Urol 2018
Take home messages mCSPC
• ADT mainstay in metastatic castration sensitive prostate cancer (Side effects!)
• Addition of Docetaxel to ADT has overall survival benefit
• Addition of Abiraterone/Pred to ADT has overall survival benefit
• Bisphosphonates (in dose/schedule to reduce incidence of SRE/SSEs) have no survival improvement and no reduction of SRE/SSEsin metastatic castration sensitive disease
• Castration-sensitive metastatic prostate cancer is a rapidly evolving field: Stay tuned: ESMO 2018!