Progression-free and overall survival in patients with ALK rearrangement–positive non–small cell lung cancer treated sequentially with crizotinib and alectinib

Abstract Introduction Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) show marked therapeutic efficacy in patients with non–small cell lung cancer (NSCLC) harboring the echinoderm microtubule-associated protein–like 4 (EML4)–ALK fusion gene. The effect on overall survival (OS) of sequential treatment with the first- and second-generation ALK-TKIs crizotinib and alectinib, respectively has remained unknown. We have now examined the clinical outcome of such sequential treatment in a retrospective analysis of patients with ALK -rearranged NSCLC. Methods Eleven patients with ALK -rearranged NSCLC treated with crizotinib followed by alectinib were identified. Progression-free survival (PFS) and OS for these patients were determined from a retrospective review of their medical records. Results Median PFS on crizotinib or alectinib was 6.1 (range, 1.0–15.4) and 15.2 (range 1.0–28.3) months, respectively. The median combined PFS for both crizotinib and alectinib was 18.2 months (range, 10.4–43.7 months). Crizotinib was continued beyond radiographic evidence of progressive disease in 6 of the 11 patients, with a median duration of postprogression crizotinib treatment of 9.4 months (range, 0–20.5 months). OS from diagnosis of metastatic disease or initiation of crizotinib treatment was 51.1 (range, 20.9–69.5) and 48.6 (range, 19.8–50.1) months, respectively. Conclusion Our retrospective study has revealed durable survival for alectinib treatment after crizotinib failure in patients with ALK -rearranged NSCLC.