Supplemental Material for: Late Emergence of Small Cell Lung Cancer during Long-Term ALK Inhibitor Therapy in ALK-Rearranged NSCLC: A Case Report

<p dir="ltr">Introduction: Rearrangements of the anaplastic lymphoma kinase (ALK) gene, predominantly involving the echinoderm microtubule-associated protein-like 4 (EML4) -ALK fusion, occur in approximately 3-7% of non-small cell lung cancers (NSCLC) and are enriched in young, never-smoking patients with lung adenocarcinoma. Among patients who relapse after ALK tyrosine kinase inhibitor (TKI) therapy, transformation to small cell lung cancer (SCLC) is estimated to occur in under 5% of cases, with a median time to transformation of 20.5 months.

In the recently reported 7-year update of the phase III CROWN study, the median progression-free survival with first-line lorlatinib had not been reached after a median follow-up of 83 months, leading to the view that ALK-rearranged lung cancer may now be regarded as a chronic disease. However, the patterns of recurrence following long-term treatment remain poorly understood.</p><p dir="ltr">Case Presentation: A 58-year-old man with stage IV ALK-rearranged lung adenocarcinoma was diagnosed with SCLC after more than 10 years of cumulative ALK-TKI therapy, comprising 7 years and 3 months of alectinib, 3 years of brigatinib, and 4 months of lorlatinib.