Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-sma
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ORIGINAL RESEARCH ARTICLE
Retrospective Observational Study of ALK‑Inhibitor Therapy Sequencing and Outcomes in Patients with ALK‑Positive Non‑small Cell Lung Cancer David M. Waterhouse1 · Janet L. Espirito2 · Marc D. Chioda3 · Bismark Baidoo2 · Jack Mardekian3 · Nicholas J. Robert2 · Elizabeth T. Masters3
© The Author(s) 2020
Abstract 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 alectinibled 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
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