Lu Shun, Zhou Jian-Ying, Niu Xiao-Min, Zhou Jian-Ya, Jian Hong, Yin Hong-Yan, Guan Sha, Wang Lin-Fang, Li Ke, He James, Su Wei-Guo
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Transl Lung Cancer Res. 2021 Feb;10(2):839-854. doi: 10.21037/tlcr-20-1028.
Fruquintinib is an oral vascular endothelial growth factor receptor inhibitor. Previous gefitinib studies with anti-angiogenics show promising efficacy. This phase II trial assessed efficacy and safety of fruquintinib in combination with gefitinib, in patients with advanced non-small cell lung cancer (NSCLC).
Fifty patients with stage IIIB/IV NSCLC and an epidermal growth factor receptor (EGFR) exon-19 deletion or exon-21 L858R mutation were enrolled between January 2017 and June 2019. Per protocol (version 1.0), patients received 4 mg fruquintinib once daily (qd) Days 1-21 of Cycle 1, using a 3-week-on/1-week-off schedule, plus continuous gefitinib 250 mg qd. If tolerated, patients proceeded to fruquintinib 5 mg qd (fruquintinib 5 mg group, n=26). Following protocol updates, dose escalation of fruquintinib from 4 mg qd to 5 mg qd was not allowed. The primary efficacy endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), disease control rate (DCR), time to response, duration of response and adverse events (AEs).
ORR was 73.5% (95% CI, 58.9-85.1) and DCR was 98.0% (95% CI, 89.2-100.0). Median PFS was 14.7 months for both groups; PFS was highest for patients with exon-19 deletion (16.5 months; 95% CI, 12.9-21.2). Grade ≥3 treatment-emergent AEs occurred in 17 (65.3%; fruquintinib 5 mg,) and 11 patients (45.8%; 4 mg). Serious AEs were recorded for nine patients (fruquintinib 5 mg, six patients; 4 mg, three).
Fruquintinib and gefitinib treatment showed an acceptable safety profile and promising efficacy in patients with NSCLC.
呋喹替尼是一种口服血管内皮生长因子受体抑制剂。先前吉非替尼联合抗血管生成药物的研究显示出有前景的疗效。这项II期试验评估了呋喹替尼联合吉非替尼治疗晚期非小细胞肺癌（NSCLC）患者的疗效和安全性。
2017年1月至2019年6月期间，纳入了50例III B/IV期NSCLC且表皮生长因子受体（EGFR）外显子19缺失或外显子21 L858R突变的患者。按照方案（版本1.0），患者在第1周期的第1 - 21天每天一次（qd）接受4 mg呋喹替尼，采用3周治疗/1周休息的方案，加用持续的吉非替尼250 mg qd。如果耐受，患者进入呋喹替尼5 mg qd组（呋喹替尼5 mg组，n = 26）。在方案更新后，不允许将呋喹替尼剂量从4 mg qd增加到5 mg qd。主要疗效终点是客观缓解率（ORR）；次要终点包括无进展生存期（PFS）、疾病控制率（DCR）、缓解时间、缓解持续时间和不良事件（AE）。
ORR为73.5%（95%CI，58.9 - 85.1），DCR为98.0%（95%CI，89.2 - 100.0）。两组的中位PFS均为14.7个月；外显子19缺失的患者PFS最长（16.5个月；95%CI，12.9 - 21.2）。≥3级治疗出现的AE在17例患者中发生（65.3%；呋喹替尼5 mg组），11例患者中发生（45.8%；4 mg组）。记录到9例严重AE（呋喹替尼5 mg组，6例患者；4 mg组，3例）。
呋喹替尼和吉非替尼治疗在NSCLC患者中显示出可接受的安全性和有前景的疗效。
