Clinical impact of switching to a second EGFR-TKI after a severe AE related to a first EGFR-TKI in EGFR-mutated NSCLC

Objective: Somatic mutations in the epidermal growth factor receptor gene are associated with a therapeutic response to epidermal growth factor receptor tyrosine kinase inhibitors such as gefitinib and erlotinib in patients with non-small cell lung cancer. Although the safety profile of these drugs is favorable, a small proportion of patients with EGFR mutation-positive non-small cell lung cancer must discontinue treatment because of adverse events such as interstitial lung disease and hepatotoxicity. Subsequent chemotherapy has not been optimized in such patients. Methods: We performed a retrospective analysis of EGFR mutation-positive non-small cell lung cancer patients who received both gefitinib and erlotinib at our institution. Patients received the second epidermal growth factor receptor-tyrosine kinase inhibitor after experiencing an adverse event or progressive disease on the first epidermal growth factor receptor-tyrosine kinase inhibitor. Results: We identified 14 patients who received both gefitinib and erlotinib in the course of their treatment. Three patients initially treated with gefitinib and two with erlotinib discontinued epidermal growth factor receptor-tyrosine kinase inhibitor therapy because of severe non-hematologic toxicity (one because of gefitinib-induced interstitial lung disease, one because of erlotinib-induced lupus erythematosus-like eruption and three because of hepatotoxicity). All five of these patients were able successfully to continue therapy with the second epidermal growth factor receptor-tyrosine kinase inhibitor with no evidence of a recurrent adverse event. Progression-free survival was significantly longer in these five patients than in the nine patients who discontinued treatment with the first epidermal growth factor receptor-tyrosine kinase inhibitor because of disease progression. Conclusions: EGFR mutation-positive non-small cell lung cancer patients who discontinue treatment with a first epidermal growth factor receptor-tyrosine kinase inhibitor because of an adverse event benefit substantially from switching to a second epidermal growth factor receptor-tyrosine kinase inhibitor before the development of drug resistance.