P3.02-042 DS-1205b, a Novel, Selective, Inhibitor of AXL, Delays the Onset of Resistance and Overcomes Acquired Resistance to EGFR-TKIs

Abstract

mutation group compared with the wild group (median 32m vs 19m) (P¼0.05). No significant survival difference between KRAS mutation and wild group was found (P>0.05). Among EGFR wild advanced NSCLC patients, the median OS of KRAS mutation group was 13 months while that of wild group was 26 months, but there was no significant difference (P>0.05). Multivariant analyzes showed gender, TKI treatment history and smoking history were independent prognostic factors in NSCLC (P<0.05). Conclusion: EGFR mutation is the most common driver gene in Chinese NSCLC, especially in adenocarcinoma patients, which often occurs in exon 19, 20 and 21 region. Then followed by KRAS mutation, it mostly occurs in exon 2. MET gene exon14 skipping is common in patients with adenocarcinoma or post-TKI treatment, which may be related to TKI resistance. Gender, smoking history and TKI treatment history could be independent prognostic factors in NSCLC.

Current Strategies for Treating NSCLC: From Biological Mechanisms to Clinical Treatment

“…Another novel selective inhibitor of AXL, DS-1205b, was reported. The combination of DS-1205b plus erlotinib/osimertinib can effectively inhibit the signaling downstream of EGFR and significantly delay the onset of tumor resistance when compared to monotherapy [ 71 ]. The effects of other AXL inhibitors (MGCD265, MGCD516, and R428) were also tested alone or combination with erlotinib in EGFR-TKI-resistant cell lines.…”