Case reportI1171 missense mutation (particularly I1171N) is a common resistance mutation in ALK-positive NSCLC patients who have progressive disease while on alectinib and is sensitive to ceritinib
Section snippets
Case
Patient is a Caucasian female never-smoker who was diagnosed with stage IV non-small cell lung cancer (left hilar tumor primary and liver metastases) at age 51. Her tumor was found to be positive for ALK rearrangement by fluorescence in situ (FISH) at the time of diagnosis. She was started on crizotinib 250 mg twice daily but had grade 3 (>5 and ≤20 upper limits of normal) liver enzymes elevation after only 3 weeks of crizotinib and requiring discontinuation of crizotinib. During the subsequent
Discussion
This case report represents only the fifth case to date demonstrating that the ALK I1171 missense mutation is an acquired resistance mechanism to alectinib and the second case to date demonstrating ALK I1171 missense mutation is sensitive to ceritinib (Table 1) [2], [3], [4]. Currently, I1171 missense mutation has developed in both EML4-ALK variant 3 [3], [4] and HIP1-ALK [3] indicating I1171 acquired resistance mutation is independent of the ALK fusion partner (Table 1). To generate the
Conflict of interest statement
Sai-Hong Ignatius Ou and Barbara Gitlitz have received honorarium as a member of the Pfizer and Roche Speaker bureau and Advisory Board.
Joel Greenbowe, Siraj Ali, Jeffrey S. Ross, Phil J. Stevens, Vincent A. Miller and employees of Foundation Medicine Inc. and own stocks of Foundation Medicine Inc.
Ziad Khan and Michele Azada have no conflict of interest to declare.
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