Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-small Cell Lung Cancer

BACKGROUND: Data are sparse concerning the sequential use of multiple anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). OBJECTIVE: This study investigated sequencing and outcomes among patients receiving multiple ALK inhibitors. PATIENTS AND METHODS: This was a retrospective observational cohort study of adult patients with ALK-positive NSCLC treated with available first- and second-generation ALK inhibitors from 1 September 2011 to 31 December 2017. Duration of therapy (DOT) and overall survival (OS) were assessed with the Kaplan–Meier method. A multivariable linear regression analysis was performed to assess if DOT with a preceding ALK inhibitor was predictive of DOT for subsequent ALK inhibitor treatments. RESULTS: A total of 410 patients were analyzed: 57% received 1 ALK inhibitor; 35%, 2 ALK inhibitors; and 8%, 3–4 ALK inhibitors. Among those receiving > 1 ALK inhibitor (n = 177), 60% received a crizotinib-led sequence and 39% an alectinib-led sequence. Nearly 60% of the overall population received chemotherapy prior to their first ALK inhibitor. Median OS for the study population was 28 months, 15 months in patients who received 1 ALK inhibitor, 42 months in patients who received 2 ALK inhibitors, and 56 months in patients who received 3–4 ALK inhibitors. Longer DOT of the first ALK inhibitor was associated with increased DOT of the second (p < 0.0001), and longer DOT of the second ALK inhibitor was associated with increased DOT of the third (p < 0.0001). CONCLUSIONS: This study provides initial information on real-world treatment patterns following the introduction of new ALK inhibitors, and supports the use of sequential ALK therapies.