非小細胞肺癌免疫治療和化學治療併用系統性回顧和統合分析、第三期臨床試驗計畫書

Immunotherapy in Combination with Chemotherapy for Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis, A Phase III Clinical Study Protocol

曾月萍(Yueh-Ping Tseng)

指導教授 ： 林家齊

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2020年)

https://doi.org/10.6342/NTU202003378

摘要

背景：
研究顯示針對第四期非小細胞肺癌患者，免疫療法合併化學療法的治療效果優於標準化療單獨使用，進行系統性文獻回顧和統合分析，探討第四期非小細胞肺癌以免疫療法合併化學療法與標準化療單獨使用的治療效果以及不良反應發生率的評估。

方法：
從電子資料庫和相關會議記錄搜尋的資料進行系統性文獻回顧和統合分析。評估免疫療法合併化學療法與標準化療單獨使用對整體存活期（OS），無惡化存活時間（PFS）的影響差異。同時評估免疫療法合併化學療法與標準化療單獨使用的不良事件發生率。

結果：
五篇研究論文和兩篇研究會議記錄進行統合分析。以免疫療法合併化學療法比上標準化療單獨使用，整體存活期的危險傷害比(Hazard ratio)和無惡化存活時間的危險傷害比皆有增加，其對應的危險傷害比分別為Hazard ratio 0.72; 95% CI, 0.61 to 0.84; p < 0.0001和Hazard ratio 0.61; 95% CI, 0.57 to 0.66; p < 0.00001；不良反應的風險比(Risk ratio)在任何等級為1.02倍 (95% CI, 1.01 to 1.04)、在3-5等級為1.15倍 (95% CI, 1.09 to 1.21)。

結論：
治療第四期非小細胞肺癌，以免疫療法合併化學治療與標準化療單獨使用比較，顯著增加整體存活期和無惡化存活時間，不良事件發生率也顯著偏高。

關鍵字

非小細胞肺癌 ； 化學療法 ； 免疫療法 ； 統合分析 ； 系統性回顧

並列摘要

Background
Studies show that immunotherapy in combination with chemotherapy had a higher efficacy benefit than chemotherapy alone as the first line treatment for stage IV non-small cell lung cancer (NSCLC) (Borghaei et al., 2019; Gandhi et al., 2018; Paz-Ares et al., 2018; Socinski et al., 2018; West et al., 2019). A systematic review and meta-analysis were conducted to explore the efficacy and adverse effects of immunotherapy in combination with chemotherapy versus chemotherapy alone for stage IV NSCLC patients.

Method
Data from electronic databases and relevant conference proceedings were obtained for analysis. The focus was to evaluate the treatment effect on the overall survival (OS) and progression free survival (PFS). In addition, adverse events were also assessed.

Results
Five studies in quantitative synthesis and two conference proceedings were used for the meta-analysis (Barlesi, 2019; Borghaei et al., 2019; Gandhi et al., 2018; Jotte, 2019; Paz-Ares et al., 2018; Socinski et al., 2018; West et al., 2019). Results show that the combined immunotherapy and chemotherapy for Stage IV NSCLC when compared with chemotherapy alone significantly increased the OS (Hazard ratio 0.72; 95% CI, 0.61 to 0.84; p < 0.0001) and PFS (Hazard ratio 0.61; 95% CI, 0.57 to 0.66; p < 0.00001). The Risk Ratio for adverse events of any grade and grade 3-5 were respectively 1.02 (95% CI, 1.01 to 1.04) and 1.15 (95% CI, 1.09 to 1.21) (Figure 4, Figure 5, Figure 6 and Figure7).

Conclusion
For Stage IV NSCLC, the combined immunotherapy and chemotherapy when compared with chemotherapy alone significantly improved the treatment effect related to OS and PFS. Moreover, the adverse events of the immunotherapy in combination with chemotherapy had a higher incidence than chemotherapy alone.

並列關鍵字

atezolizumab ； chemotherapy ； immunotherapy ； meta-analysis ； non–Small cell lung cancer ； pembrolizumab ； systematic review

參考文獻

Barlesi, F. (2019). IMpower132: efficacy of atezolizumab + carboplatin/cisplatin + pemetrexed as 1L treatment in key subgroups with stage IV non squamous NSCLC

Borghaei, H., Langer, C. J., Gadgeel, S., Papadimitrakopoulou, V. A., Patnaik, A., Powell, S. F., . . . Gandhi, L. (2019). 24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. J Thorac Oncol, 14(1), 124-129. doi:10.1016/j.jtho.2018.08.004

Bray, Jacques Ferlay, M., Isabelle Soerjomataram, M., MSc, PhD., Rebecca L. Siegel, M., Lindsey A. Torre, M., Ahmedin Jemal, P., DVM. (2018). Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA CANCER J CLIN, 68, 394–424. doi:10.3322/caac.21492.

Cao, R., Ma, J. T., Zhang, S. L., Sun, L., Liu, Y., Zhang, X. Y., . . . Han, C. B. (2019). Rational application of the first-line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta-analysis. Cancer Medicine, 8(11), 5033-5046. doi:10.1002/cam4.2407

Doherty, M. (2019). Pembrolizumab alone or with chemotherapy for PDL1 positive NSCLC: A network meta-analysis of randomized trials. Journal of Clinical Oncology, 37. doi:10.1200/JCO.2019.37.15_suppl.9087