Durable response to alectinib in metastatic pulmonary adenocarcinoma with a rare TFG-ALK fusion in a non-Asian patient: A case report

Background Anaplastic lymphoma kinase (ALK) rearrangements occur in approximately 1–2% of non–small cell lung cancers (NSCLC). While most ALK-positive tumors harbor EML4‑ALK fusions, an increasing number of rare ALK fusion partners are being described. For many of these rare fusions, there is limited information regarding their oncogenic relevance and sensitivity to ALK tyrosine kinase inhibitors (ALK‑TKIs). Case presentation We report the case of a 47‑year‑old never‑smoking Caucasian woman who presented with multiple supra‑ and infratentorial brain metastases and a pulmonary mass in the left lower lobe. Bronchoscopic biopsies revealed a poorly differentiated, micropapillary, TTF‑1‑positive pulmonary adenocarcinoma. Next‑generation sequencing (NGS) detected a very rare TFG::ALK fusion, and PD‑L1 expression was 5% on tumor cells. First‑line treatment with alectinib 600 mg twice daily led to a pronounced systemic and intracranial response with near‑complete remission of the primary tumor and metastases after 6 months. The therapy was well tolerated, with only mild transient rash and liver enzyme elevation. After 17 months, a slight progression of a single parietal brain metastasis was successfully treated with stereotactic radiotherapy, while alectinib was continued. At the most recent follow‑up, the patient had sustained disease control for 54 months. Conclusion This case illustrates a deep and durable systemic and intracranial response to alectinib in metastatic pulmonary adenocarcinoma harboring a rare TFG::ALK fusion. It underscores the importance of comprehensive molecular testing, including NGS, to identify uncommon but actionable ALK fusions and provides clinical evidence that TFG::ALK-positive NSCLC can be sensitive to alectinib.