| 摘要: | 目的：肺癌的發生率及死亡率在所有癌別排名中居高不下。治療肺癌的方式隨著醫藥科技進步，除了傳統的化學治療以及標靶治療外，免疫檢查點抑制劑已是目前對於腫瘤缺乏驅動因子突變且 Programmed death ligand1(PDL-1) 表現量為陽性的晚期非小細胞肺癌標準治療之一。相關研究證實 Pembrolizumab 合併含鉑劑之化學治療法對於晚期非小細胞肺癌治療有顯著的臨床效益，但所需的治療費用也相當可觀，台灣目前尚未有相關之經濟效益參考文獻。本研究以 台灣中央健康保險署觀點評估 Pembrolizumab 合併化學治療 (Pembrolizumab combination組) 相較傳統含鉑化學合併療法 (Chemotherapy combination組)用於治療第一線轉移性非鱗狀非小細胞肺癌的成本效益。方法：本研究使用分區生存分析模型 (Partitioned-survival analysis model) 模擬時間長度為10 年。存活分析曲線模型模擬 KEYNOTE-189 臨床試驗 (研究對象需至少 18 歲以上，為轉移 性非鱗狀非小細胞肺癌患者(stage 4)，先前未接受系統性化學治療且無 EGFR、ALK 等驅動因 子突變)中無疾病惡化存活曲線 (Progression-fee survival) 及整體存活曲線 (Overall survival)。 生活品質校正年 (Quality-adjusted life-year,QALY) 的數值計算源自於 KEYNOTE-189 臨床試 驗使用 EQ-5D量表對受試者進行調查的效用值結果。費用包含：療程費用、二線療程費用、 疾病處置費用、PD-L1檢測費用、臨終照護費用以及副作用處置費用。每年對成本和健康結果 的折現率是3%。使用決定性敏感度分析及機率性敏感度分析測試成本效益結果的穩健程度。 願付價格訂為三倍國民人均生産毛額，相當於新台幣 2,788,290 元。 結果：基本案例情境下，Pembrolizumab combination 組相較 Chemotherapy combination 組可多增加 0.89 個 QALY，但須多花費新台幣 2,201,203 元，遞增成本效果比值(Incremental costeffectiveness ratio, ICER)為新台幣 2,478,601 元/QALY。而在 PD-L1 表現量 ≥ 50% 次族群分析中， Pembrolizumab combination 組相較 Chemotherapy combination 組可多增加 1.12 個 QALY，但須多花費新台幣 2,522,528 元，ICER 值為新台幣 2,258,358元/QALY。 結論：Pembrolizumab 合併化學療法對於第一線治療轉移性非鱗狀非小細胞肺癌相較傳統的標 準化學合併療法具有成本經濟效益，尤其以 PD-L1 表現量 ≥ 50% 次族群分析結果更為顯著。
Objectives：The incidence and mortality rate of lung cancer is still high among all cancer. Along with the advances in medical technology, in addition to traditional chemotherapy and targeted therapy, immune checkpoint inhibitors are currently one of the standard treatment for non-small cell lung cancer that lacks driver mutations in tumors and is positive for programmed death ligand 1 (PD-L1) . Although many studies have confirmed that Pembrolizumab combined with chemotherapy has significant clinical benefits for the treatment of advanced non-small cell lung cancer, but the treatment costs are also considerable. There is no relevant economic benefit reference literature in Taiwan. Our aims were to evaluate the cost effectiveness of pembrolizumab plus chemotherapy (Pembrolizumab combination) compared with standard-of-care platinum-based chemotherapy (Chemotherapy combination) as first-line treatment in metastatic non-squamous non-small-cell-lung cancer in Taiwan third-party public healthcare payer perspective. Method：We made a research by a partitioned-survival model and estimated time horizon for 10 years. Survival Model were used Kaplan-Meier curves estimates of progression-free survival and overall survival curves from the KEYNOTE-189 clinical trial (patients aged ≥ 18 years with stage IV non-squamous NSCLC, without epidermal growth factor receptor (EGFR)-activating mutations or anaplastic lymphoma kinase (ALK) translocations, and haven’t received systemic chemotherapy before). Quality adjusted life-years (QALYs) were based on utility values by progression status calculated from the KEYNOTE-189 trial. Costs for regimen-related costs, disease management costs, second-line therapy costs, end of life care costs and adverse event management costs were included. Cost and utility were discounted at 3% per year. Use probabilistic sensitivity and deterministic sensitivity analyses to test the robustness of the results. The willingness to pay is 3 times the gross domestic product (GDP) , which is equivalent to NT$2,788,290. Result：In the base-case scenario , Pembrolizumab combination resulted in an expected gain of 0.89 QALYs , and incremental cost of NT$2,201,203 compared with chemotherapy combination. The incremental cost-effectiveness ratio (ICER) is NT$2,478,601/QALY. And the scenario analysis of PD-L1 expression level ≥ 50% group, the Pembrolizumab combination can increase 1.12 QALYs more than the chemotherapy combination group, incremental cost is NT$2,522,528, and the ICER value is NT$2,258,358/QALY. Conclusion：Pembrolizumab combination provides cost-effective option compared with chemotherapy combination as first-line treatment in metastatic non-squamous nonsmall- cell-lung cancer , especially in the PD-L1 expression level ≥ 50% sub-group analysis results are more significant. |
