CHICAGO—A Phase 3 study demonstrated that icotinib provides comparable efficacy to oral gefitinib, but with a better safety profile, in patients with non-small cell lung cancer (NSCLC) who had progressed after one or two lines of therapy, according to a presentation at the American Society of Clinical Oncology’s 2011 Annual Meeting. Icontinib is a potent and selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)

Yan Sun, MD, of Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, and colleagues studied 399 patients with NSCLC who progressed after one or two chemotherapy regimens. The patients were randomized to receive icotinib 150mg 3 times daily (n=199) or gefitinib 250mg once daily (n=196). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), time-to-progression (TTP), quality of life (QOL), and safety.

PFS in the icotinib arm was a median 35 days longer than gefitinib (137 days vs. 102 days; hazard ratio [HR] 0.84; 95% CI [0.67–1.05]). Secondary endpoints for icotinib vs. gefitinib, respectively: median OS 419 days vs. 467 days (HR 0.997 [0.776-1.281]; ORR: 27.6% vs. 27.2%; DCR 75.4% vs. 74.9%).

Adverse response rate in icotinib group was 60.5%, which was significantly lower than that in the gefitinib group (70.4%; P=0.04). Specifically, 40.0% of patients in the icotinib group developed rash compared with 49.2% in the gefitinib group; 18.5% of icotinib patients had diarrhea compared to 27.6% in gefitinib group (P=0.03); 8% patients in the icotinib arm had elevated transaminase levels vs. 12.6% in gefitinib group. EGFR gene mutational analysis was performed on 132 patients.

Mutations were identified in 68 patients, among which 29 were in icotinib arm and 39 were in gefitinib arm. The ORR and PFS in both groups demonstrated significant differences between patients with mutations (M) and patients with the wild type gene (W). In the icotinib group, M vs. W was 58.6% (17/29) and 5.1% (2/39) for ORR and 198 days and 70 days for PFS. In the gefitinib group, M vs. W was 53.8% (21/39) and 3.1% (1/27) for ORR and 158 days and 67 days for PFS.

EGFR gene mutational analysis was performed by using DsX Scorpion ARMS. The investigators stated that of 88 kinases profiled, icotinib powerfully inhibited EGFR and its three mutants, with no meaningful inhibition of the other kinases tested. This study was designed to show that icotinib is not inferior to gefitinib in this patient population.