Clinical impact of sequential treatment with ALK-TKIs in patients with advanced ALK-positive non-small cell lung cancer: Results of a multicenter analysis

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.