ALK fusion + TP53 mutation

Functional analysis demonstrated that TTN mutations were enriched the complement and coagulation cascades, which correlated with the pathway of cell adhesion, migration, and proliferation. Conclusions Collectively, the histologic subtypes of invasive LUAD were genetically different, and certain trunk genotypes might synergize with branching TTN mutation to develop highly aggressive components.

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.