PP01.09 Genotypic Characteristics and Resistance Mutations in Advanced ALK+ NSCLC: The ALK-PATHFINDER Study

Abstract

ALK rearrangements occur in approximately 5% of advanced non-small cell lung cancer (NSCLC) patients. The current standard initial therapy is a second-generation ALK tyrosine kinase inhibitor (TKI), such as alectinib or brigatinib, which has shown great improvements in response rates, progression-free survival and overall survival. However, most patients relapse due to acquired resistance mechanisms including secondary mutations in ALK kinase domain, such as G1202R and I1171N. Indeed, ALK mutations are more frequent in patients treated with second generation inhibitors than with first-generation (53-54% under alectinib or ceritinib, 71% under brigatinib vs. 20% under crizotinib). In addition, the optimal sequence of ALK inhibitors has not been established yet, but the selection of the most suitable subsequent line according to ALK resistance mutations must be a key strategic approach for the therapeutic decision-making process for these patients.