Stage 4 ALK-positive lung cancer: remission on lorlatinib

What happened, in summary

A 35-year-old man presented with chronic cough, persistent bilateral lower chest and rib pain, and unintentional weight loss. Chest CT and PET/CT showed bilateral pulmonary nodules, mediastinal adenopathy, skeletal lesions, and liver lesions, consistent with metastatic disease; no CNS metastases were present at that time. Biopsy of a liver lesion confirmed adenocarcinoma with signet-ring features. Because endoscopy and colonoscopy did not identify a gastrointestinal primary, immunohistochemistry was used to confirm non-small cell lung cancer of adenocarcinoma subtype, with TTF-1 positivity. Genomic testing found an ALK-positive rearrangement. He began alectinib 600 mg orally twice daily, but myalgias and creatine kinase elevation above 10 times the upper limit of normal required dose reduction to 450 mg twice daily. Disease stayed stable until surveillance brain MRI showed new CNS oligometastatic disease. Treatment was changed to brigatinib, and he was referred for stereotactic radiosurgery with Gamma Knife. In October 2021, progressive brain metastasis despite SRS and brigatinib led the team to consider whole-brain radiation therapy. Before proceeding, they started lorlatinib monotherapy and paused the whole-brain radiation plan. Six months later, brain MRI showed marked improvement. PET/CT in January 2022 showed absence of PET avidity in the original liver, skeletal, mediastinal, and pulmonary lesions, favoring treated metastatic disease. This sequence matters clinically because the main setback was isolated CNS progression after earlier ALK-directed therapy, not uncontrolled systemic disease. Chemotherapy and surgery were not part of this phase of care. He continued in radiologic and clinical disease remission on lorlatinib, with whole-brain radiation avoided in the reported course.