OBJECTIVES: Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer 
(NSCLC) is sensitive to treatment with an ALK-tyrosine kinase inhibitor (-TKI). 
However, the benefit of sequential treatment with a 2nd ALK-TKI in patients who 
fail a 1st ALK-TKI has been poorly addressed.
MATERIALS AND METHODS: We collected the data of 69 advanced ALK-positive NSCLCs 
who were treated with one or more ALK-TKIs at three Italian institutions. The 
clinical outcome of treatment with an ALK-TKI and the patterns of treatment upon 
failing a 1st ALK-TKI were recorded.
RESULTS: Objective response rate (ORR) and median progression-free survival 
(PFS) on a 1st ALK-TKI (mostly crizotinib) were 60.9% and 12 months, 
respectively. Of the 50 patients who progressed on a 1st ALK-TKI, 22 were 
further treated with a 2nd ALK-TKI (either ceritinib or alectinib), for whom an 
ORR of 86.4% and median PFS of 7 months, respectively, were reported. 
Conversely, 13 patients underwent rapid clinical/radiographic disease 
progression leading to death shortly after discontinuation of the 1st ALK-TKI, 7 
patients were managed with a 1st ALK-TKI beyond progression, and 8 patients 
transitioned to other systemic treatments (mostly chemotherapy). 
Post-progression survival (PPS) significantly favored the 22 patients who were 
sequentially treated with a 2nd ALK-TKI over those who transitioned to other 
systemic treatments (P=0.03), but not versus those who were treated with a 1st 
ALK-TKI beyond progression (P=0.89).
CONCLUSION: Sequential treatment with a 2nd ALK-TKI is effective in patients who 
fail a 1st ALK-TKI. Continuous ALK-inhibition upon failing a 1st ALK-TKI may be 
associated with improved clinical outcome.