Response to Crizotinib Re-administration After Progression on Lorlatinib in a Patient With ALK-rearranged Non–small-cell Lung Cancer

Abstract

Clinical Practice Points•Non–small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangement is sensitive to ALK-tyrosine kinase inhibitors (TKIs). First- and second-generation ALK-TKIs are effective for ALK-rearranged NSCLC; however, resistance to ALK-TKI treatment arises.•Lorlatinib is a third-generation ALK-TKI and shows clinical activity for patients who have undergone previous ALK-TKI treatment. Although the response to lorlatinib was observed, eventually, acquired resistance to lorlatinib occurs, and post-lorlatinib treatment has not been determined.•We present a case of ALK-rearranged NSCLC in a patient who responded to crizotinib re-administration after progression on lorlatinib. Although tumor heterogeneity, exposure of several therapies, and the limited small tissue samples can impact measurements of MET expression, phospho-MET was up-regulated focally in post-lorlatinib tissue compared with pre-lorlatinib tissue, suggesting that resistance to lorlatinib and the subsequent response to re-administration of crizotinib after progression on lorlatinib might be partly related to MET pathway activation.•Re-administration of crizotinib following lorlatinib might enhance the better prognosis of patients with ALK-rearranged NSCLC. •Non–small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangement is sensitive to ALK-tyrosine kinase inhibitors (TKIs). First- and second-generation ALK-TKIs are effective for ALK-rearranged NSCLC; however, resistance to ALK-TKI treatment arises.•Lorlatinib is a third-generation ALK-TKI and shows clinical activity for patients who have undergone previous ALK-TKI treatment. Although the response to lorlatinib was observed, eventually, acquired resistance to lorlatinib occurs, and post-lorlatinib treatment has not been determined.•We present a case of ALK-rearranged NSCLC in a patient who responded to crizotinib re-administration after progression on lorlatinib. Although tumor heterogeneity, exposure of several therapies, and the limited small tissue samples can impact measurements of MET expression, phospho-MET was up-regulated focally in post-lorlatinib tissue compared with pre-lorlatinib tissue, suggesting that resistance to lorlatinib and the subsequent response to re-administration of crizotinib after progression on lorlatinib might be partly related to MET pathway activation.•Re-administration of crizotinib following lorlatinib might enhance the better prognosis of patients with ALK-rearranged NSCLC.