免疫檢查點抑制劑作為非小細胞肺癌病人第二線治療之研究

Abstract

1. 研究簡介 背景 歐洲紫杉醇（docetaxel）於1999年是第一個被美國FDA核准用於非小細胞肺癌（non-small cell lung cancer, NSCLC）第二線治療的藥物，並自此成為標準療法之一。然而，免疫檢查點疫制劑（immune checkpoint inhibitors）例如：anti-PD-1 or PD-L1 antibodies 的發展，其對病人較佳的存活益處和較低的毒性，對於晚期非小細胞肺癌的治療帶來很大的進步。 目的 本研究的目的主要是透過系統性文獻回顧和統合分析的方式，來整合評估免疫檢查點疫制劑（anti-PD-1 or PD-L1 antibodies）作為非小細胞肺癌第二線治療之整體有效性及安全性，納入分析的試驗將以隨機對照試驗為主。 2. 研究方法 資料搜尋策略 於2019年11月中至12月初經由PubMed/Medline電子資料庫進行文獻搜尋，使用的關鍵字為non-small cell lung cancer AND PD-L1 OR PD-1 AND docetaxel，並以Clinical Trial來篩選搜尋結果。 3. 研究結果 總共有5個符合條件的試驗納入統合分析。研究結果顯示，整體存活時間（overall survival, OS）在anti-PD-1 or PD-L1 antibodies治療組優於docetaxel 治療組（HR=0.72, 95% CI= 0.64-0.81, p=0.000），且在anti-PD-1 or PD-L1 antibodies治療組也有較佳的目標治療反應率（objective response rate, ORR）（OR=1.75, 95% CI= 1.33-2.31, p=0.000）。然而，無疾病惡化存活（progression-free survival, PFS）於兩種治療組的比較卻沒有達到統計上的顯著差異（HR=0.89, 95% CI= 0.77-1.02, p=0.088）. 此外，anti-PD-1 or PD-L1 antibodies 治療相關的不良事件，無論在所有等級（OR=0.33, 95% CI=0.28-0.39, p=0.000）或第3和第4等級嚴重程度（OR=0.17, 95% CI=0.26-0.10, p=0.000）的事件，均少於化學治療組。 4. 研究結論 對於先前治療但失敗或疾病惡化的非小細胞肺癌病人，免疫檢查點疫制劑如anti-PD-1 or PD-L1 antibodies作為二線治療確實可改善病人的存活，且有較佳的抗腫瘤效果，並提供了良好的安全性。

1. Introduction Rationale Docetaxel was the first drug approved by FDA in 1999 as the second-line therapy in non-small cell lung cancer patients, and has been the standard of care since then. However, the development of immune checkpoint inhibitors such as anti-PD-1 or PD-L1 antibodies have been a great advance in treating advanced NSCLC, which have shown better surviv-al benefit and safety profile. Objective The aim of this systematic review and meta-analysis of randomized controlled trials is to evaluate the efficacy and safety of Immune checkpoint inhibitors (anti-PD-1 or PD-L1 antibodies）as second-line treatment in previously treated NSCLC patients. 2. Methods Search strategy Literature search was performed through the electronic database of PubMed/Medline between mid-November and early December 2019 by using keywords related to the PI-CO elements. The following keywords were used: non-small cell lung cancer AND PD-L1 OR PD-1 AND docetaxel, and are filtered by Clinical Trial. 3. Results Five studies were selected for the meta-analysis. Pooled analysis of OS (HR=0.72, 95% CI= 0.64-0.81, p=0.000) and ORR (OR=1.75, 95% CI= 1.33-2.31, p=0.000) fa-vored anti-PD-1 or PD-L1 antibodies. However, the analysis of PFS did not reach statis-tical significance (HR=0.89, 95% CI= 0.77-1.02, p=0.088). In addition, the analysis showed that anti-PD-1 or PD-L1 antibodies group has fewer TRAEs than docetaxel group, either in terms of any grade (OR=0.33, 95% CI=0.28-0.39, p=0.000) or grade 3/4 events (OR=0.17, 95% CI=0.26-0.10, p=0.000). 4. Conclusion Immune checkpoint inhibitors such as anti-PD-1 or PD-L1 antibodies could enhance the survival benefit and antitumor response as second-line treatment for previously treated advanced NSCLC. They also provide favorable safety profile.