A randomized, double-blind phase III study of icotinib versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy (ICOGEN).

Abstract

7522 Background: Icotinib is a potent and selective EGFR-TKI. Of 88 kinases profiled, Icotinib (Ic) powerfully inhibited EGFR and its 3 mutants, with no meaningful inhibition of the rest of kinases tested. This study was designed to show that Ic is not inferior to Gefitinib (Ge). Methods: Patients (Pts) with NSCLC progressed after one or two lines of chemotherapies were randomized to receive Ic (150mg Tid) or Ge (250mg Qd). The primary endpoint was PFS. The second endpoints were OS, ORR, TTP, QOL and tolerance. EGFR gene mutational analysis was performed by using DsX Scorpion ARMS. Results: From Feb 2009 to Nov 2010, 399 patients were randomized to receive either Ic (200) or Ge (199). Baseline characteristics were well balanced between the two arms . Ic demonstrated 35 day (d) median PFS extension compared to Ge (Ic vs. Ge: 137 d vs. 102, HR 0.84, 95% CI 0.67-1.05), reaching the primary objective of non-inferiority. With 49.4% maturity, OS was similar between Ic and Ge groups (median OS was 504 d and 531 d, respectively). Furthermore, ORR (Ic vs. Ge: 27.6% vs. 27.2%), DCR (75.4% vs. 74.9%), TTP (156 d vs. 111 d ) and QoL (101.4± 9.6 vs. 103.0± 19.1) were comparable between Ic and Ge groups. Adverse response rate in Ic group was 60.5%, which was significantly lower than that in Ge group (70.4%) (P=0.04). Specifically, 39.5% pts in Ic developed rash compared to 49.2% in Ge; 18.5% pts in Ic had diarrhea compared to 27.6% in Ge (P=0.03); 8.0% pts in Ic had elevated transaminase level compared to 12.6% in Ge. EGFR gene mutational analysis was performed for 132 pts. Mutations were identified in 66 pts (50%), among which 27 (40.9%) were in Ic and 39 (59.1%) were in Ge. The ORR and PFS in both Ic and Ge groups demonstrated significant differences between pts with mutations (M) and pts with the wild type gene (W). In the Ic group, M vs. W was 59.3% (16/27) vs. 5.1% (2/39) for ORR and 198 d vs. 70 d for PFS. In the Ge group it was 52.6% (20/39) vs. 3.7% (1/27) for ORR and 158 d vs. 76 d for PFS. Conclusions: This study demonstrated that Icotinib provides similar efficacy to Gefitinib, but with better tolerability, in NSCLC patients previously treated with one or two chemotherapy agents.