Lorlatinib as an Alternative to CNS Radiotherapy in Patients with NSCLC − Case Studies
Two remarkable case studies from authors at the Netherlands Cancer Institute Antoni van Leeuwenhoek in Amsterdam present patients with advanced NSCLC with metastatic CNS involvement. Treatment with crizotinib led to good control of pulmonary involvement but did not affect metastatic CNS involvement. The introduction of lorlatinib subsequently led to rapid improvement in neurological symptoms, which was also confirmed by CNS imaging.
ALK Tyrosine Kinase Inhibitors in NSCLC Treatment
In a subset of patients with non-small cell lung cancer (NSCLC), there is a translocation of the ALK gene (for anaplastic lymphoma kinase). Treatment with tyrosine kinase inhibitors effective on ALK-activated signaling pathways (ALK-TKIs) leads to a prolonged progression-free survival (PFS). Lorlatinib is a third-generation ALK-TKI with improved CNS availability, indicated for patients refractory to first- and second-generation ALK-TKI treatment.
In the Czech Republic, lorlatinib is approved for the treatment of patients with advanced ALK-positive NSCLC who have experienced disease progression during treatment with alectinib or ceritinib (second-generation ALK-TKIs), crizotinib (first-generation ALK-TKI), or another ALK-TKI. The recommended dose is 100 mg once daily per os.
Case Descriptions
Patient 1
A 48-year-old woman was diagnosed with NSCLC in the left lower lung lobe at clinical stage IV. Molecular analysis of a cervical lymph node confirmed the presence of an ALK translocation. The patient began therapy with crizotinib, and a CT scan after 1 month of treatment showed regression of both pulmonary and extrapulmonary involvement. However, there was an elevation in tumor marker levels.
Despite the absence of neurological symptoms, a brain MRI was performed, revealing numerous metastases in the right parietal and occipital lobes, along with hydrocephalus. Concurrently, there was further regression of pulmonary involvement.
The patient began therapy with ceritinib, but after only 11 days of treatment, she developed right arm paresis followed by a consciousness disorder due to obstructive hydrocephalus. Despite dexamethasone therapy and a ventriculoperitoneal shunt, the patient fell into a coma, and lorlatinib was administered via a nasogastric tube.
After just 2 days of lorlatinib treatment, there was a reduction in neurological symptoms and a decrease in tumor marker levels. After a month of treatment, full consciousness was restored, and significant improvement in arm paresis was observed. After a year of lorlatinib treatment, the patient had minimal neurological symptoms, brain MRI did not demonstrate the presence of metastases, and the primary lung tumor was regressing.
Patient 2
A 54-year-old man was diagnosed with stage IV NSCLC in the right lower lobe. After 4 months of crizotinib treatment, there was partial regression of intrathoracic involvement. After more than a year of treatment, the disease gradually progressed, and crizotinib was replaced with brigatinib. Two months into the treatment, the patient began experiencing headaches, nausea, vomiting, and right arm paresthesia. Brain MRI revealed the presence of cerebral and leptomeningeal metastases. Subsequently, lorlatinib treatment was initiated, and symptoms resolved within a few days.
After a year of lorlatinib treatment, brain MRI showed regression of metastases, lung CT indicated slight progression of the primary tumor, but without clinical symptoms, so the treatment continued.
Conclusion
Administration of lorlatinib led to rapid improvement in neurological symptoms in patients who experienced CNS disease progression during second-generation ALK-TKI treatment. Therefore, lorlatinib therapy may be considered as an alternative to brain radiotherapy in patients with rapid CNS metastasis progression of NSCLC during second-generation ALK-TKI treatment.
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Sources:
- Gafer H., de Waard Q., Compter A., van den Heuvel M. Rapid regression of neurological symptoms in patients with metastasised ALK+ lung cancer who are treated with lorlatinib: a report of two cases. BMJ Case Rep 2019; 12 (7): e227299, doi: 10.1136/bcr-2018-227299.
- SPC Lorviqua. Available at: www.ema.europa.eu/en/documents/product-information/lorviqua-epar-product-information_cs.pdf
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