Routine-Dose and High-Dose Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Exon 21-L858R Mutation: the Randomized, Phase II, INCREASE Trial

• Published in: Clinical cancer research Vol. 26; no. 13; pp. 3162 - 3171
• Main Authors: Li, Xi, Zhang, Li, Jiang, Da, Wang, Yan, Zang, Aimin, Ding, Cuimin, Zhao, Min, Su, Wuyun, Zhang, Yan, Zhong, Diansheng, Wu, Jin, Zhang, Cuiying, An, Guangyu, Hu, Xingsheng, Cheng, Gang, Wang, Huaqing, Li, Yongqun, He, Xiaohui, Liu, Junli, Liang, Li, Ding, Lieming, Mao, Li, Zhang, Shucai
• Format: Journal Article
• Language: English
• Published: United States 01.07.2020
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-19-3064

Our primary purpose is to explore safety and efficacy of high-dose icotinib in comparison with routine-dose icotinib in patients with non-small cell lung cancer (NSCLC) harboring 21-L858R mutation. Patients with treatment-naïve, EGFR-mutant (21-L858R or exon 19 deletion at 2:1) NSCLC were enrolled. Patients with 21-L858R mutation were randomized to receive routine-dose icotinib (125 mg, thrice daily; L858R-RD) or high-dose icotinib (250 mg, thrice daily; L858R-HD), whereas patients with exon 19 deletion received only routine-dose icotinib (19-Del-RD) until progression, death, or unacceptable toxicity. The primary endpoint was median progression-free survival (mPFS), assessed by an independent review committee. From May 2015 to November 2017, 253 patients (86 in L858R-RD; 90 in L858R-HD; and 77 in 19-Del-RD) were enrolled. The mPFS in L858R-HD group was similar to that in 19-Del-RD group (12.9 months and 12.5 months, respectively) and was significantly longer than that in L858R-RD group [12.9 months vs. 9.2 months, hazard ratio (HR): 0.75; 95% confidence interval (CI), 0.53-1.05]. A longer but statistically nonsignificant mPFS was observed between 19-Del-RD and L858R-RD groups (12.5 months vs. 9.2 months, HR: 0.80; 95% CI, 0.57-1.13). A higher objective response rate (ORR) was observed in L858R-HD group compared with L858R-RD group (73% vs. 48%), also between 19-Del-RD and L858R-RD groups (75% vs. 48%). Similar incidences of grade 3/4 toxicities were observed among the three treatment groups. High-dose icotinib improved mPFS and ORR in patients with NSCLC harboring 21-L858R mutation with acceptable tolerability, which could be a new therapeutic option for this patient population.