Table 1.

Impact of distinct ALK kinase domain mutations on the sensitivity of ALK-rearranged NSCLC tumors/cell lines to FDA-approved ALK TKIs

CrizotinibCeritinibAlectinib
G1123SRRS
1151TinsRNDaND
L1152RRRS
C1156YRRbS
I1171T/N/SRSR
F1174CRRND
F1174LRRS
F1174VRRS
V1180LRSR
L1196MRSS
L1198FSRR
G1202RRRR
S1206YRSS
G1269ARSS
  • Abbreviations: ND, not determined; R, resistant; S, sensitive.

  • aResistance to ceritinib was observed in vitro in Ba/F3 cells engineered to express 1151Tins (33), but partial response was observed in a patient with compound G1269A and 1151Tins mutations treated with ceritinib (45).

  • bIn patients with resistance to ceritinib, C1156Y co-occurred with other ALK mutations (13).