建議

本研究為針對國內對於使用 temsirolimus 於治療晚期腎細胞癌之成本效益分析，

但所蒐集之參數部分因取得不易而以國外參數代替。因此，期待未來研究可以增加與著重 國內參數的取得及運用，以提升研究結果並更趨於國內真實之現況與需求。

雖然本研究藉由決策模式計算方案間之遞增成本效益比(ICER)以進行經濟評估，可獲 知使用 temsirolimus 作為治療晚期腎細胞癌的方案將不具有成本效益，但對於未來進行相 關藥物或健康照護介入方案的成本效益分析研究之建議，若能增加評估方案之預算衝擊的 分析，以提供一個更完備的成本效益評估範本，將可增加健康照護政策決策者對於方案在 療效與成本之間的考量依據。

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表一、美國癌症聯合委員會(American Joint Committee of Cancer, AJCC)腎細胞癌 TNM 系統分類表

Stage Description

TX Primary tumor cannot be assessed T0 No evidence of primary tumor

T1 Tumor < 7 cm in greatest dimension, limited to kidney T1a Tumor ≤ 4 cm in greatest dimension, limited to kidney

T1b Tumor > 4 cm but ≤ 7 cm in greatest dimension, limited to kidney T2 Tumor > 7 cm in greatest dimension, limited to kidney

T3 Tumor extends into major veins or invades adrenal gland or perinephric tissues, but not beyond Gerota’s fascia T3a Tumor invades adrenal gland or perinephric tissues, nut not beyond Gerota’s fascia

T3b Tumor grossly extends into renal vein(s) or vena cava below diaphragm T3c Tumor grossly extends into vena cava above diaphragm

T4 Tumor invades beyond Gerota’s fascia NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis

N1 Metastasis in a single regional lymph node N2 Metastasis in more than one regional lymph node MX Distant metastasis cannot be assessed

M0 No distant metastasis M1 Distant metastasis

Note - Adapted from current of American Joint Committee on Cancer (2008)

表二、美國癌症聯合委員會(AJCC)腎細胞癌分期表

Stage Grouping Stage T Stage N Stage M

I T1 N0 M0

II T2 N0 M0

III T1 N1 M0

T2 N1 M0

T3 N0 M0

T3 N1 M0

IV T4 N0 M0

T4 N1 M0

Any T N2 M0

Any T Any N M1

Note - Adapted from current of American Joint Committee on Cancer (2008)

表三、腎細胞癌五年存活率

Disease Extent TNM Stage 5-Years Survival Rate (%)

All organ-confined T1-T2 N0 M0 70-90

≦ 4 cm T1a N0 M0 90-100

> 4 but < 7 cm T1b N0 M0 80-90

≧ 7 cm T2 N0 M0 70-80

Invasion of perinephric fat T3a N0 M0 60-80

Adrenal involvement T3a N0 M0 0-30

Venous involvement T3b-T3c N0 M0 40-65

Locally advanced T4 N0 M0 0-20

Lymphatic involvement Any T, N+, M0 0-20 Systemic metastasis Any T, any N, M1 0-10

American Joint Committee on Cancer. AJCC cancer staging manual 2002

表四、轉移性腎細胞癌之分子標靶藥物第三期臨床詴驗療效整理表

ORR = objective response rate; PFS = progression-free survival; OS = overall survival; qd = once daily; IFN-α = interferon-α; tiw = three times weekly; HR = hazard ratio; bid = twice daily;

* The primary OS end point was confounded by required crossover after disease progression.;

** OS after data from patients who crossed over from comparator to active treatment were censored.;

# Temsirolimus versus IFN-a versus temsirolimus plus IFN-a.

表五、轉移性腎細胞癌藥物療效彙整表

Objective response Progression-free survival

Hormone treatment 2% N/A

Chemotherapy 5-6% N/A

Interleukin-2 21-33% (95%CI 15-33, high-dose); 10% (low-dose)

3.1 months

Interferon-α 10-15% 4.7 months (4.1-5.3) Sunitinib 30-45% in both

cytokine-refractory and treatment-naïve patients

11 months (10-12) in treatment-naïve patients (phase III trial); 8.4 months in cytokine-refractory patients (pooled phase II trial data)

Sorafenib 2-10% 5.7 months in treatment-naïve patients; 5.5 months in cytokine-refractory patients Bevacizumab 10-13% as monotherapy;

26-31% in combination with interferon

8.5 months (7.5-9.7) in treatment-naïve patients as monotherapy; 10.2 months in treatment-naïve patients in combination with interferon; 4.8 months in

cytokine-refractory patients

Temsirolimus 7-9% 3.7 months in monotherapy arm and combination arm in treatment-naïve patients (phase III trial); 5.8 months in treatment-refractory patients (randomized phase II trial with different doses)

N/A=not applicable

表六、國外 Temsirolimus 成本效益分析結果 - Holey et al. (2010)

Interferon

-α

Temsirolimus Temsirolimus vs. Interferon

-α

Life years 1.07 1.52 0.45

QALYs 0.53 0.77 0.24

Time on treatment (months) 4.6 7.6 3.0

Drug cost £ 2,823 £ 18,036 £ 15,213

Drug admin £ 367 £ 6,215 £ 5,848

Medical management* £ 729 £ 1,176 £ 447

BSC in PD £ 2,599 £ 3,422 £ 822

Total costs £ 6,519 £ 28,849 £ 22,331

Cost/LYG £ 49,701

Cost/QALY £ 94,632

* CT scans, monitoring, blood tests.

BSC, best supportive care; CT, computed tomography; LYG, life years gained; PD, progressive disease; QALY, quality-adjusted life year.

表七、國外 Temsirolimus 單維敏感性分析結果 - Holey et al. (2010)

Base-case Sensitivity analysis ICERs

General

Base-case 3.5% p.a. costs and benefits n/a £ 94,632

Discounting 3.5% p.a. costs and benefits 0% p.a. costs and benefits £ 90,072

10 years 5 years £ 105,798

Efficacy

HR PFS 0.74 0.60 (lower 95% CI) £ 114,878

0.91 (upper 95% CI) £ 75,591

HR OS 0.73 0.60 (lower 95% CI) £ 56,589

0.91 (upper 95% CI) £ 254,146

Cost

Cost of temsirolimus £ 620 per vial £ 465 per vial (25% reduction) £ 75,523

£ 372 per vial (40% reduction) £ 64,058

Utilities

Utilities 0.60 PFS, 0.45 PD 0.78 PFS, 0.70 PD* £ 67,060

PFS utility 0.48 (lower 95% CI) £ 107,233 PFS utility 0.72 (upper 95% CI) £ 84,681 PD utility 0.37 (lower 95% CI) £ 101,785 PD utility 0.52 (upper 95% CI) £ 88,571

表八、轉移性腎細胞癌各藥物之成本效益研究結果

Controller Comparator

Incremental Cost-effectiveness Ratio (ICER)

PFS LY QALYs

Bevacizumab +

Interferon-α Interferon-α + Placebo £ 74,999

Temsirolimus Interferon-α £ 55,814

Sunitinib Interferon-α $18,611 $ 67,215 $ 52,593

Sorafenib* BSC £ 90,630

Sunitinib* BSC £ 37,519

PFS: progression free survival; LY: life-years; QALYs: quality adjusted life years

*: second line treatment for mRCC; BSC: best supporttive care

表九、本研究所採用之 Weibull curve parameters

Parameter Interferon-α Temsirolimus

Progression-free survival λ 0.542 0.401

γ 0.582 0.582

Overall survival λ 0.127 0.092

γ 0.829 0.829

表十、本研究兩比較方案中之藥物成本

Drug Brand Dose and frequency Cost

Interferon-α Roferon-A 3 MU 3 times at first week NT$ 418 per 3 MU NT$ 1,254 first model cycle 9 MU 3 times at secondary week NT$ 630 per 4.5 MU NT$ 3,780 secondary cycle 18 MU 3 times per future week NT$ 842 per 6 MU NT$ 30,312 future cycle Temsirolimus Torisel 25 mg once per week NT$ 45,000 per dose NT$ 180,000 per cycle

表十一、本研究兩比較方案中之非藥物成本

Cost item Treatment Base-case cost Base-case cost per 4-week

model cycle

Drug administration Interferon-α NT$ 59 for out patient administration. One

administration every two weeks.

NT$ 164 for drug administration. One administration per cycle.

NT$ 284

Temsirolimus NT$ 2154 per administration. One administration per week

NT$ 39.5 per heparin dose, one dose per month

NT$ 8,567

CT scans Interferon- α and temsirolimus NT$ 5,480 per scan, one scan every two months NT$ 2,740 Monitoring Interferon- α and temsirolimus NT$ 222 per doctor visit, one visit every two weeks NT$ 444 Blood tests Interferon- α and temsirolimus NT$ 380 per test, one test per month NT$ 380 BSC in PD Interferon- α and temsirolimus NT$ 222 per doctor visit, one visit every two

weeks. Narcotic analgesics and central analgesics for BSC, drug includes morphine 10 mg qid, fentanyl patch 25ug or 50 ug q3d, tramadol 50 mg qid.

NT$ 4,347

表十二、模式確認

LY of Interferon-α

LY of

Temsirolimus Ince. LY QALYs of Interferon-α

QALYs of

Temsirolimus Ince. QALYs

Hoyle (2010) 3.5% 1.07 1.52 0.45 0.53 0.77 0.24

本研究 3.5% 1.04 1.49 0.45 0.52 0.76 0.24

LY: life-years; QALYs: quality adjusted life years

Ince. LY: incremental life-years; Ince.QALYs: incremental quality adjusted life years

表十三、本研究折現前之成本結果

Interferon-α Temsirolimus Temsirolimus vs. Interferon-α

Drug cost NT$123,528 NT$ 1,268,628 NT$ 1,145,100

Drug admin NT$ 678 NT$ 60,400 NT$ 59,722

Medical management NT$ 15,004 NT$ 25,098 NT$ 10,094

BSC in PD NT$ 37,980 NT$ 51,672 NT$ 13,692

Total costs NT$ 177,190 NT$ 1,405,798 NT$ 1,228,608

表十四、本研究成本使用 3%折現率後之結果

Interferon-α Temsirolimus Temsirolimus vs. Interferon-α

Drug cost NT$ 90,463 NT$ 1,200,709 NT$ 1,110,246

Drug admin NT$ 649 NT$ 57,146 NT$ 56,497

Medical management NT$ 13,912 NT$ 23,775 NT$ 9,683

BSC in PD NT$ 35,683 NT$ 47,671 NT$ 11,988

Total costs NT$ 140,706 NT$ 1,329,301 NT$ 1,188,595

表十五、本研究折現前之成本效益結果

QALY INCE. QALY LY INCE. LY COST INCE. COST ICER/QALY ICER/LY

Interferon- 0.55 1.10 NT$ 177,190

Temsirolimus 0.82 0.27 1.62 0.51 NT$ 1,405,789 NT$ 1,228,607 NT$ 4,585,959 NT$ 2,401,738

LY: life-years; QALYs: quality adjusted life years

Ince. LY: incremental life-years;Iince.QALYs: quality adjusted life years

表十六、本研究以 3%折現後之成本效益結果

QALY INCE.

QALYs

LY INCE. LY COST INCE. COST ICER/QALYs ICER/LY

Interferon- 0.52 1.05 NT$ 169,019

Temsirolimus 0.77 0.24 1.51 0.46 NT$ 1,328,871 NT$ 1,159.852 NT$ 4,775,609 NT$ 2,512,048

LY: life-years; QALYs: quality adjusted life years

Ince. LY: incremental life-years; Ince.QALYs: incremental quality adjusted life years

表十七、本研究單維敏感性分析結果

Base-case Sensitivity analysis ICERs

General

Base-case 3% p.a. costs and benefits n/a NT$ 4,775,609

Discounting 3% p.a. costs and benefits 0% p.a. costs and benefits NT$ 4,585,959 5% p.a. costs and benefits NT$ 4,898,128

10 years 5 years NT$ 5,527,085

Cost of temsirolimus NT$ 45,000 per 25 mg/vial NT$ 40,500 per 25 mg/vial (10%

reduction) PFS utility 0.48 (lower 95% CI) NT$ 5,399,893 PFS utility 0.72 (upper 95% CI) NT$ 4,280,713 PD utility 0.37 (lower 95% CI) NT$ 5,162,892 PD utility 0.52 (upper 95% CI) NT$ 4,481,462

* Taken from Motzer et al. (2007)

表十八、本研究機率性敏感度分析參數分佈設定

Parameter Distribution

Hazard Ratio (HR) lognormal distribution

Utility beta distribution

Non Drug Cost gamma distribution

Briggs A. et al., Decision Modeling for Health Economic Evaluation (2006)

圖一、本研究之馬可夫模式(Markov Model)健康狀態圖

圖二、本研究預測晚期腎細胞癌接受藥物治療之 Weibull survival curve

圖三、本研究治療方案之成本百分比

圖四、The Cost-Effectiveness Plane

圖五、本研究兩種治療方案間之可接受曲線

圖六、The Cost-Effectiveness Plane

ICER: NT$ 1,667,280

圖七、使用 temsirolimus 治療方案之年度各項成本百分比

附錄一、本研究以 Excel 2007 模擬 temsirolimus 治療曲線下陎積之計算結果

31 0.2049 0.0519 0.1530 9,725.34 0.1875 0.0076

67 0.0496 0.0097 0.0399 1,707.78 0.0416 0.0017

103 0.0137 0.0026 0.0111 419.75 0.0105 0.0004

附錄二、本研究以 Excel 2007 模擬干擾素-α 治療曲線下陎積之計算結果

28 0.1338 0.0231 0.1107 1,161.71 0.1224 0.0049

64 0.0185 0.0022 0.0162 123.35 0.0155 0.0006

100 0.0031 0.0004 0.0027 18.72 0.0024 0.0001

cIFNdisc ILYdisc hcIQALYdisc

169,019

1.05

0.52

在文檔中 使用Temsirolimus治療晚期腎細胞癌之成本效益分析 (頁 56-96)