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

Abstract

Purpose:Our primary purpose is to explore safety and efficacy of high-dose icotinib in comparison with routine-dose icotinib in non-small cell lung cancer (NSCLC) patients harboring 21-L858R mutation. Experimental Design:Treatment-naïve, EGFR-mutant (21-L858R or exon 19 deletion at 2:1) NSCLC patients were enrolled. Patients with 21-L858R mutation were randomized to receive routine-dose icotinib (125mg, thrice daily; L858R-RD) or high-dose icotinib (250mg, 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 (IRC). Results: From May, 2015 to November, 2017, 253 patients (86 in L858R-RD; 90 in L858R-HD; 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 to 1.05). A longer but statistically non-significant 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 to 1.13). A higher objective response rate (ORR) was observed in L858R-HD group compared to 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. Conclusions:High-dose icotinib improved mPFS and ORR in NSCLC patients harboring 21-L858R mutation with acceptable tolerability, which could be a new therapeutic option for this patient population.