A case of STRN-ALK fusion positive lung adenocarcinoma treated with lorlatinib monotherapy

Anaplastic lymphoma kinase (ALK) rearrangements occur in 3-5% of non-small cell lung cancer (NSCLC), with the STRN-ALK fusion representing a rare variant with variable responses to ALK tyrosine kinase inhibitors (TKIs). Lorlatinib, a third-generation ALK TKI with broad activity against resistance mutations and superior CNS penetration, has not been previously reported in STRN-ALK fusion-positive NSCLC. We present a 52-year-old male never-smoker who initially complained of back pain and was found to have multiple thoracic lesions on a CT scan of the chest, pleural nodules and a pleural effusion, which was found to be consistent with exudative effusion and adenocarcinoma on cytology. He was diagnosed with stage IV lung adenocarcinoma with signet-ring cell features. Next-generation sequencing of tissue identified a STRN-ALK fusion along with pathogenic ARID1A and KMT2D mutations. The patient was initiated on lorlatinib 100 mg daily as first-line therapy. Treatment was complicated by manageable adverse events, including hyperlipidemia, peripheral neuropathy, first-degree AV block, and lower extremity edema. At nine-month follow-up, PET-CT demonstrated a partial response with resolution of bone metastases and a significant reduction in thoracic lesions. This represents the first reported case of STRN-ALK fusion-positive NSCLC treated with lorlatinib monotherapy, demonstrating the clinical efficacy and tolerability of third-generation ALK inhibition for this rare fusion variant, which has variable responses to earlier-generation TKIs in the literature. These findings support lorlatinib as an effective treatment option for STRN-ALK NSCLC, particularly given its superior CNS penetration, which is particularly relevant for preventing or treating brain metastases in patients with previously identified brain metastases.