Personalized Approach to Therapy Selection in a Patient with ALK-Positive Non-Small Cell Lung Cancer: A Clinical Case

Abstract

Anaplastic lymphoma kinase-positive non-small cell lung cancer (ALK-positive NSCLC) is a molecularly defined subtype of lung cancer in which the optimal sequencing of systemic therapy is essential for achieving long-term disease control. Progression involving the central nervous system (CNS) represents a particular clinical challenge, as intracranial disease control becomes an independent and important treatment objective. The aim of this study was to demonstrate the potential of an individualized approach to treatment selection in a patient with ALK-positive NSCLC who received several consecutive lines of therapy with ALK inhibitors, including lorlatinib after CNS progression. The clinical case was described using data from the patient’s medical history, computed tomography and magnetic resonance imaging, morphological, immunohistochemical, and molecular genetic examinations, multidisciplinary team decisions, and information on systemic and radiation therapy. A 40-year-old patient was diagnosed with ALK-positive NSCLC of the lower lobe of the right lung, stage IIIB (T4N2M0). Following disease progression after platinum-based chemotherapy, sequential targeted therapy with crizotinib and ceritinib was administered. When multiple brain metastases developed, the patient received symptomatic radiation therapy followed by chemotherapy. In February 2024, treatment with lorlatinib was initiated. This therapy resulted in clinical improvement, stabilization of the pulmonary lesions, and positive radiological dynamics according to follow-up brain MRI. The presented case highlights the importance of timely molecular profiling, regular assessment of CNS involvement, multidisciplinary decision-making, and personalized selection and sequencing of ALK inhibitors. Lorlatinib may provide effective systemic and intracranial disease control after progression during previous lines of treatment.