驱动基因突变阳性的非鳞非小细胞肺癌的免疫治疗

治疗线数	Ⅰ级推荐	Ⅱ级推荐	Ⅲ级推荐
晚期一线治疗 a
晚期二线及以上治疗 b，c	信迪利单抗 + 贝伐珠单抗类似物  +化疗（1A 类）d#

#. 已纳入国家医保目录。

【注释】

a    从目前已有的研究来看，并不支持驱动基因突变阳性的晚期 NSCLC 患者一线使用免疫治疗。

b     一项 meta 分析比较了PD-1/PD-L1 抑制剂与多西他赛治疗晚期NSCLC 的疗效与安全性，共纳入3 项临床试验，包括CheckMate 057、KEYNOTE-010 和 POPLAR 研究［49］。结果显示，在 EGFR敏感突变阳性人群中，多西他赛组的疗效优于 PD-1/PD-L1 抑制剂，提示EGFR 突变患者后线使用免疫治疗，其获益并没有超越化疗。OAK 研究也得到类似结论，其亚组分析显示，EGFR突变患者并未从二线阿替利珠单抗治疗中获得OS 的显著改善。ATLANTIC 是第一个在 EGFR/ ALK+ 患者中评价ICIs疗效的前瞻性研究［50］。在队列 1 中，入组111 例 EGFR/ALK+ 患者，其中可评估的 PD-L1 ≥25% 的患者有74 例，仅9 例（12.2%） 取得客观缓解。

c   IMpower150 研究纳入了 124 例 EGFR 突变和 ALK 重排的非鳞 NSCLC 患者，亚组分析结果［51］显示，对于 EGFR 敏感突变患者，与贝伐珠单抗+ 化疗组相比，阿替利珠单抗+ 贝伐珠单抗 +化疗组的生存显著获益，PFS 中位数分别为10.3 个月 vs. 6.1 个月（HR=0.41；95% CI0.23~0.75）， OS 中位数分别为 29.4 个月 vs. 18.1 个月（HR=0.60；95% CI 0.31~1.14）。IMpower151 研究结果显示，驱动基因阳性组 PFS 相似，在野生组间出现差异。

d     基于 ORIENT-31 研究，NMPA已批准信迪利单抗联合贝伐珠单抗及化疗治疗经EGFR-TKI 治疗失败的EGFR 基因突变阳性的局部晚期或转移性非鳞状 NSCLC，故本指南将其升级为Ⅰ级推荐。ORIENT-31 研究［52］是一项评估信迪利单抗联合或不联合贝伐珠单抗类似物及化疗用于经 EGFR-TKI 治疗进展的EGFR 突变的局部晚期或转移性非鳞 NSCLC 的有效性和安全性的随机、双盲、多中心Ⅲ期临床研究。信迪利单抗 + 贝伐珠单抗联合化疗组（试验组 A），信迪利单抗联合化疗组（试验组 B） 和化疗组（对照组 C） 的随访时间中位数分别为 12.9 个月、15.1 个月和 14.4 个月。基于独立影像评估委员会（IRRC） 评估，三组PFS 中位数（95% CI） 分别为 7.2（6.6~9.3） 个月、5.5（4.5~6.1） 个月和 4.3（4.1~5.3） 个月。相比对照组C，试验组 A 与试验组 B的 PFS 保持显著获益（HR=0.51，95% CI 0.39~0.67，P < 0.0001）（HR=0.72，95% CI0.55~0.94，P=0.016）。生存分析显示试验组 A 有一定生存获益趋势，OS：21.1 个月 vs.19.2个月， HR=0.98，调整交叉治疗影响后，OS HR 在 0.79~0.84之间。组间安全性可控， ≥ 3 级 AEs发生率（56%vs. 41% vs. 49%）。

参考指南：

中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会 (CSCO) 免疫检查点抑制剂临床应用指南2024.人民卫生出版社.北京 2024

参考指南：
中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会 (CSCO) 免疫检查点抑制剂临床应用指南2024.人民卫生出版社.北京 2024

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