A case of ALK-rearranged non-small cell lung cancer that responded to ceritinib after development of resistance to alectinib

Abstract

The second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) alectinib and ceritinib are standard treatment options for patients with non-small cell lung cancer (NSCLC) positive for ALK fusion genes. However, almost all patients eventually develop resistance to these drugs. We here report a case of ALK-rearranged NSCLC that developed resistance to alectinib but remained sensitive to ceritinib. The L1196M mutation within the ALK fusion gene was detected after failure of consecutive treatment with crizotinib and alectinib, but no other mechanism underlying acquired resistance to ALK-TKIs was found to be operative. Given the increasing application of ALK-TKIs to the treatment of patients with ALK-rearranged NSCLC, further clinical evaluation is warranted to provide a better understanding of the mechanisms of acquired resistance to these agents and to inform treatment strategies for such tumors harboring secondary mutations.