阿帕替尼联合吉非替尼作为晚期EGFR突变非小细胞肺癌的一线治疗：III期临床研究（CTONG1706）
Apatinib plus gefitinib as first-line treatment in advanced EGFR-mutant non-small cell lung cancer: thephase IIIACTIVE study(CTONG1706)（Journal of Thoracic Oncology；IF:13.357） Hongyun Zhao, MD, Wenxiu Yao, MD, Xuhong Min, BS, Kangsheng Gu, MD, Guohua，Yu, BS, Zhonghan Zhang, MS, Jiuwei Cui, MD, Liyun Miao, MD, Li Zhang, MS, Xia，Yuan, MD, Yong Fang, MD, Xiuhua Fu, MS, Chengping Hu, PhD, MD, Xiaoli Zhu,MD, Yun Fan, MD, Qitao Yu, MS, Gang Wu, MD, Ou Jiang, MD, Xiuping Du, MD,Jiwei Liu, MD, Wei Gu, MS, Zhiguo Hou, MS, Quanren Wang, PhD, Rongrong Zheng,MS, Xianfeng Zhou, PhD, Li Zhang, MD. Journal of Thoracic Oncology 2021Introduction 介绍Blocking vascular endothelial growth factor (VEGF) pathway can enhance the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). ACTIVE is the first phase III study conducted in China, evaluating apatinib, a VEGFR2 TKI, plus gefitinib as first-line therapy in EGFR-mutant NSCLC.阻断血管内皮生长因子（VEGF）通路可以增强表皮生长因子受体（EGFR）酪氨酸激酶*制剂抑**（TKIs）在EGFR突变型非小细胞肺癌（NSCLC）中的作用。ACTIVE是首个在中国进行的III期研究，评估阿帕替尼，一种VEGFR2 TKI，联合吉非替尼作为EGFR突变型NSCLC的一线治疗药物的效果。 Methods 方法Treatment-naïve patients with stage IIIB/IV non-squamous NSCLC, an ECOG PS of 0/1 and EGFR ex19del or ex21L858R mutation were randomized 1:1 to receive oral gefitinib (250 mg/day), plus apatinib (500 mg/day; A+G group) or placebo (P+G group). Stratification factors: mutation type, sex and PS. The primary endpoint was PFS by blinded independent radiology review committee (IRRC). Secondary endpoints: investigator-assessed PFS, OS, quality of life (QoL), safety, etc. Next-generation sequencing was used to explore efficacy predictors and acquired resistance.未经治的IIIB / IV期非鳞状非小细胞肺癌，ECOG PS为0/1和EGFR ex19del或ex21L858R突变的患者按1：1的比例随机接受口服吉非替尼（250 mg /天）加阿帕替尼（500 mg /天，A + G组）或安慰剂（P + G组）。分层因素：突变类型，性别以及PS评分。主要起点是由独立设盲的放射学审查委员会（IRRC）评估的无进展生存时间（PFS）。次要起点：研究者评估的PFS，总生存期（OS），生活质量（QoL），安全性等。二代测序被用于用于探究功效果测指标以及获得性耐药。 Results 结果313 patients were assigned to the A+G (n=157) or P+G group (n=156). Median IRRC-PFS in the A+G group was 13.7 months vs 10.2 months in the P+G group (HR 0.71; P=.0189). Investigator- and IRRC-assessed PFS were similar. OS was immature. The most common treatment-emergent adverse events ≥grade 3 were hypertension (46.5%) and proteinuria (17.8%) in the A+G group and increased ALT (10.4%) and AST (3.2%) in the P+G group. QoL in the two groups had no statistical differences. Post-hoc analysis showed PFS benefits tended to favor the A+G group in patients with TP53 ex8 mutation.共313例患者被分配至A + G组（n = 157）或P + G组（n = 156）。A + G组的IRRC-PFS中位数为13.7个月，而P + G组为10.2个月（HR 0.71；P = .0189）。研究者和IRRC评估的PFS相似。总生存时间的资料尚不能完整收集。≥3级的最常见的治疗治疗相关不良反应在A + G组为高血压（46.5％）和蛋白尿（17.8％），在P + G组为ALT（10.4％）和AST（3.2％）升高。两组的生活质量无统计学差异。事后分析显示，A+G组的TP53 ex8突变患者倾向于在无进展生存时间上获益。 Conclusions 结论Apatinib+gefitinib as first-line therapy demonstrated superior PFS in advanced EGFR-mutant NSCLC vs placebo+gefitinib. Combination therapy brought more adverse events but did not interfere QoL.阿帕替尼+吉非替尼作为一线治疗药物在晚期EGFR突变NSCLC中表现出优于安慰剂+吉非替尼的无进展生存时间。联合疗法带来了更多的不良反应，但并没有干扰生存质量。