Topic 7.
Use of osteoclast-targeted therapy for skeletal related events (SRE)/
symptomatic skeletal events (SSE) prevention for metastatic CRPC
(mCRPC; not for osteoporosis/ bone loss)
空格結果≧75%（達到St. Gallen共識）標示黃底紅字；空格結果≧50%標示紅字。
第三次
臺灣晚期攝護腺癌專家共識
3 rd Taiwan Advanced Prostate Cancer Consensus
121
Survey URO RO MO High Vol Senior UO N
Option 1 Option 2
有關在使用osteoclast-targeted therapy的治療時間該維持多久，國內外專家並無共識。
國外專家近7成選擇大約使用兩年。國內專家各約佔一半。zoledronic acid 的pivotal trial (Saad et al., J Natl Cancer Inst 2002)的劑量是8 mg q3w for 15 month。而denosumab 的pivotal trial (Fizazi et al., Lancet 2011)，則是每4周投與一次，平均投予41個月。
目前並沒有對於osteoclast-targeted therapy的最佳治療時間長短的研究。但是在study 中可以觀察到，ONJ的發生比率是隨著用藥時間加長而增加 (Stopeck et al., Support Care Cancer 2016)。
•評論分析：
175 42%
58%
46 68%
32%
30 46%
54%
96 43%
57%
95 53%
47%
30 39%
61%
When you use osteoclast-targeted therapy (zoledronic acid or denosumab) in men with mCRPC and bone metastases, what treatment duration do you recommend?
Q7-1
Survey Panelists 164
46%
54%
22 65
336 44%
56%
1 1
Responders
1. Approximately 2 years 2. Indefinitely
3. Abstain (including I do not use osteoclast-targeted therapy in this setting)
Non-responder, unqualified to answer
St.Gallen 48 68%
32%
6 0
122
Survey URO RO MO High Vol Senior UO N
Option 1 Option 2 Option 3
175 5%
66%
29%
46 0%
70%
30%
30 0%
63%
38%
96 7%
72%
21%
95 6%
72%
22%
30 3%
83%
14%
mCRPC病患若在使用osteoclast-targeted therapy的期間發生ONJ，國內外專家一致有共 識的會永久停用osteoclast- targeted therapy。
許多專家在要不要使用osteoclast-targeted therapy也有許多討論，尤其在mCRPC的 studies，novel AR targeted agents (Abi/Enza)都顯示出可以減少SRE。Abiraterone減少 39% SRE發生率(Logothetis et al., Lancet Oncol 2012)。Enzalutamide減少31% SRE發 生率(Fizazi et al., ESMO 2012 abstract 8960)。
•評論分析：
What do you recommend for the majority of men with mCRPC and multiple bone metastases who develop osteonecrosis of the jaw while on osteoclast-targeted therapy for SRE/SSE prevention?
Q7-2
Survey Panelists 165
4%
66%
30%
86
37 0 92%
8%
1
Responders
1. Continue osteoclast-targeted therapy
2. Discontinue osteoclast-targeted therapy permanently 3. Discontinue osteoclast-targeted therapy and re-start after complete wound healing
Non-responder, abstain, unqualified to answer
St.Gallen 449
0 84%
16%
1
123
Survey URO RO MO High Vol Senior UO N
Option 1 Option 2 Option 3 Option 4 Option 5
175 17%
29%
19%
27%
10%
46 20%
40%
15%
25%
0%
30 21%
46%
13%
17%
4%
31 21%
46%
13%
17%
4%
95 22%
30%
14%
27%
8%
30 14%
21%
21%
39%
4%
After you read the recommendation made by 2015 St. Gallen APCCC “ DO NOT treat a man with metastatic castration-naive prostate cancer with bisphosphonates or denosumab in the dose established for reduction of risk of skeletal-related events or symptomatic skeletal events in patients with CRPC. Instead, adequate calcium and vitamin D supplementation, lifestyle changes, and bisphosphonates or denosumab at a lower dose or schedule for the prevention of osteoporosis or osteoporotic fractures should be considered.” Will you still prescribe bisphosphonates or denosumab for patients with metastatic castration-naive prostate cancer?
2015 St Gallen專家建議改以採取天然食物補充Vit D或預防骨質疏鬆的低劑量bisphospho- nates or denosumabe給予mHSPC病患。不建議使用mCRPC劑量在mHSPC的病患上。國內專家 也有共識，在大多數的mHSPC病患，會選擇使用低劑量的bisphosphonates or denosumab。
•評論分析：
Q7-3
Survey Panelists 155
18%
32%
17%
25%
8%
96
37 0
70%
16%
8%
5%
1
Responders
1. Yes, in the majority of patients with full dose and schedule as mCRPC
2. Yes, in the majority of patients but with dose and schedule as for the prevention of osteoporosis or osteoporotic fractures 3. Only for patients with history of SRE with full dose and schedule as mCRPC
4. Only for patients with history of SRE but with dose and schedule as for the prevention of osteoporosis or osteoporotic fractures 5. Will not prescribe anymore
Non-responder, abstain, unqualified to answer
124
