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演示文稿, 科学出版物 | 2019-09-09

WCLC 2019: 呋喹替尼治疗晚期非小细胞肺癌(FALUCA)III期试验

MA14.05 – A Randomized Phase III Trial of Fruquintinib Versus Placebo in Patients with Advanced Non-Small Cell Lung Cancer (FALUCA)

 

Venue: IASLC 2019 World Conference on Lung Cancer in Barcelona, Spain
Session:MA14 – The Adequate MTarget Is Still the Issue
Date: Monday, September 09, 2019
Time: 15:45-17:15
Presenter: Shun Lu
Authors: Gongyan Chen, Yuping Sun, Sanyuan Sun, Jianhua Chang, Yu Yao, Zhendong Chen, Feng Ye, Junguo Lu, Jianhua Shi, Jianxing He, Xiaoqing Liu, Yiping Zhang, Zhihua Liu, Jian Fang, Ying Cheng, Chunhong Hu, Weidong Mao, Yanping Hu, Youling Gong, Li Shan, Zhixiong Yang, Yong Song, Wei Li, Chong Bai, buhai Wang, Rui Ma, Zhendong Zheng, Mingfang Liu, Zhijun Jie, Lejie Cao, Wangjun Liao, Hongming Pan, Dongning Huang, Yuan Chen, Jinji Yang, Shukui Qin, Shenglin Ma, Li Liang, Zhe Liu, Jianying Zhou, Min Tao, Yijiang Huang, Feng Qiu, Yunchao Huang, Ye Hua, Yiping Chen, Weiguo Su

 

Background

Fruquintinib, an orally active kinase inhibitor that selectively targets vascular endothelial growth factor (VEGF) receptor, demonstrated significant benefit in progression-free survival and disease control in a randomized Phase II study in patients with non-small-cell lung cancer (NSCLC) who had failed two lines of chemotherapy. This Phase III FALUCA trial is a randomized, double-blind, placebo-controlled, multicenter trial designed to confirm the efficacy in the same patient population (NCT02691299).

Method

From December 2015 to February 2018, 45 clinical centers across China participated in the trial. A total of 730 patients aged 18-75 with advanced NSCLC who had failed two lines of chemotherapy were screened and 527 who met the eligibility criteria were enrolled into the study. Patients were stratified based on epidermal growth factor receptor mutation status and prior use of VEGF inhibitor therapy, and were randomized in a 2:1 ratio to receive fruquintinib (n=354) or placebo (n=173) once daily in a 3 weeks on/1 week off 4-week cycle. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response. The final data cutoff was on September 21, 2018.

Result

Median OS was 8.94 months for fruquintinib and 10.38 months for placebo (hazard ratio, 1.02; 95% CI, 0.816 to 1.283; p=0.841). Median PFS was 3.68 months for fruquintinib comparing to 0.99 months for placebo, respectively (hazard ratio, 0.34; 95%CI, 0.279 to 0.425; p<0.001). The ORR and DCR were 13.8% and 66.7% for fruquintinib, compared with 0.6% and 24.9% for placebo (both p<0.001), respectively. The most frequent treatment-emergent adverse events with fruquintinib (≥grade 3) were hypertension (20.7%), hand-foot syndrome (11.0%), and proteinuria (1.4%). A sensitivity analysis revealed that median OS was significantly prolonged with fruquintinib compared with placebo in patients who received no subsequent systemic anti-tumor therapies (7.00 months versus 5.06 months ; hazard ratio, 0.64; 95%CI, 0.453 to 0.903; p=0.010).

Conclusion

The FALUCA trial failed to meet the primary end point of OS while confirming significant benefit in secondary end points including PFS, ORR and DCR. The safety profile of fruquintinib in this patient population was acceptable and consistent with that identified in the Phase II study. A post-hoc sensitivity analysis revealed that the anti-tumor therapies that patients received post disease progression probably contributed to the failure of this study on the primary end point.