JCO Glob Oncol. 2026 Jun;12(6):e2500574. doi: 10.1200/GO-25-00574. Epub 2026 Jun 24.
ABSTRACT
PURPOSE: There are now six anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) approved for first-line ALK-positive non-small cell lung cancer (NSCLC) therapy, improving survival and quality of life. However, real-world data on treatment outcomes, predictors of discontinuation, and sequencing strategies remain scarce, while direct comparisons between second- and third-generation TKIs are limited.
METHODS: This global longitudinal observational study evaluated patients with ALK-positive NSCLC, with data collected via online surveys from September 2022 to April 2025. Treatment patterns, outcomes, and factors associated with time to discontinuation (TTD) were assessed using descriptive statistics and univariable regression.
RESULTS: Overall, 1,111 patients from 71 countries were included (64% female; median age at diagnosis 53 years; 28% with a smoking history). Crizotinib was predominantly the first TKI administered, although prescribing patterns shifted over time (crizotinib before 2016, alectinib between 2017 and 2022, and lorlatinib thereafter). After the follow-up period (median of 20.7 months), 60% of patients remained on their initial TKI, with TTD varying significantly across agents. Factors associated with prolonged TTDs included radiotherapy, prior chemotherapy, delayed therapy initiation, and treatment in India (crizotinib) and retirement, prior chemotherapy, and treatment in the United Kingdom (alectinib). Gastroesophageal reflux disease, thyroid disease, TP53 mutations, and ALK V3a/b fusions were associated with a short TTD. Globally, alectinib to lorlatinib was the most common treatment sequence. Discontinuations because of toxicity were the highest with crizotinib and ceritinib and the lowest with lorlatinib and alectinib.
CONCLUSION: This multinational registry-based analysis highlights evolving global treatment patterns, supports newer TKIs’ effectiveness, and identifies clinical and molecular factors associated with treatment duration.
PMID:42341251 | DOI:10.1200/GO-25-00574
