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.
Hanna et al. (Sun,) studied this question.