Large-scale comparative analysis of clinico-genomic characteristics, treatment outcomes and resistant mechanisms of ALK/ROS1/RET-rearranged non-small cell lung cancer (NSCLC) in a nationwide genomic screening project (LC-SCRUM-Asia/TRY). (ASCO 2023)
TP53 mutation was associated with shorter OS in all three fusions (mOS [TP53 mt+/mt-] ALK; 35.7 vs. 108.8, p < 0.01, ROS1; 26.4 vs. 47.4, p = 0.06, RET; 28.9 vs. 76.1 months, p = 0.05), shorter PFS with first line alectinib in ALK (mPFS [TP53 mt+/mt-] 11.0 vs. 38.4 months, hazard ratio [HR] 2.5 [95% CI, 1.5-4.2], p < 0.01) and shorter PFS with initial crizotinib in ROS1 (mPFS [TP53 mt+/mt-] 5.8 vs. 25.2 months, HR 2.6 [95% CI, 1.3-4.8], p < 0.01). There was no significant difference in PFS with first-line platinum plus pemetrexed among fusions (mPFS 12.6 vs. 10.7 vs. 9.2 months) and PFS with initial immune checkpoint inhibitors among fusions (mPFS 3.9 vs. 5.1 vs. 3.0 months)... Pts with ALK/ROS1/RET-rearranged NSCLC shared similar characteristics, but the occurrence of concomitant mutations was lower in ALK than in ROS1 and RET. TP53 mutation was associated with worse prognosis in pts with ALK/ROS1/RET-rearranged NSCLC. Among those received TKI, pts with ALK-rearranged NSCLC had better prognosis than those with ROS1 and RET-rearranged NSCLC.