Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706)
Hongyun Zhao, Wenxiu Yao, Xuhong Min, Kangsheng Gu, Guohua Yu, Zhonghan Zhang, Jiuwei Cui, Liyun Miao, Li Zhang, Xia Yuan, Yong Fang, Xiuhua Fu, Chengping Hu, Xiaoli Zhu, Yun Fan, Qitao Yu, Gang Wu, Ou Jiang, Xiuping Du, Jiwei Liu, Wei Gu, Zhiguo Hou, Quanren Wang, Rongrong Zheng, Xianfeng Zhou, Li Zhang, Hongyun Zhao, Wenxiu Yao, Xuhong Min, Kangsheng Gu, Guohua Yu, Zhonghan Zhang, Jiuwei Cui, Liyun Miao, Li Zhang, Xia Yuan, Yong Fang, Xiuhua Fu, Chengping Hu, Xiaoli Zhu, Yun Fan, Qitao Yu, Gang Wu, Ou Jiang, Xiuping Du, Jiwei Liu, Wei Gu, Zhiguo Hou, Quanren Wang, Rongrong Zheng, Xianfeng Zhou, Li Zhang
Abstract
Introduction: Blocking vascular endothelial growth factor pathway can enhance the efficacy of EGFR tyrosine kinase inhibitors in EGFR-mutant NSCLC. ACTIVE is the first phase 3 study conducted in the People's Republic of China evaluating apatinib, a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, plus gefitinib as first-line therapy in EGFR-mutant NSCLC.
Methods: Treatment-naive patients with stage IIIB or IV nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and EGFR exon 19 deletion or exon 21 L858R mutation were randomized 1:1 to receive oral gefitinib (250 mg/d), plus apatinib (500 mg/d; apatinib [A] + gefitinib [G] group), or placebo (placebo [P] + gefitinib [G] group). Stratification factors were mutation type, sex, and performance status. The primary end point was progression-free survival (PFS) by blinded independent radiology review committee (IRRC). Secondary end points were investigator-assessed PFS, overall survival, quality of life (QoL), safety, etc. Next-generation sequencing was used to explore efficacy predictors and acquired resistance.
Results: A total of 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 versus 10.2 months in the P + G group (hazard ratio 0.71, p = 0.0189). Investigator- and IRRC-assessed PFS were similar. Overall survival was immature. The most common treatment-emergent adverse events greater than or equal to grade 3 were hypertension (46.5%) and proteinuria (17.8%) in the A + G group and increased alanine aminotransferase (10.4%) and aspartate aminotransferase (3.2%) in the P + G group. QoL in the two groups had no statistical differences. Post hoc analysis revealed PFS benefits tended to favor the A + G group in patients with TP53 exon 8 mutation.
Conclusions: Apatinib + gefitinib as first-line therapy had superior PFS in advanced EGFR-mutant NSCLC versus placebo + gefitinib. Combination therapy brought more adverse events but did not interfere QoL.
Trial registration: NCT02824458.
Keywords: Apatinib; Epidermal growth factor receptor; Non–small cell lung cancer; Targeted therapy; Vascular endothelial growth factor.
Copyright © 2021. Published by Elsevier Inc.
Source: PubMed