Successful Pregnancy and Healthy Baby Outcome in a Patient With Tyrosine Kinase Inhibitor-Refractory ALK-Positive NSCLC and Central Nervous System Metastasis Treated With Lorlatinib With Maternal-Fetal Pharmacokinetics and Child Milestone Development Correlations.

INTRODUCTION: Lorlatinib is the preferred first-line treatment for advanced ALK+ (ALK+) NSCLC on the basis of the 5-year CROWN update. However, the effects of lorlatinib on the fetus and neonate remain unknown.

METHODS: We report the first case of a patient with metastatic ALK+ NSCLC who became pregnant during treatment with lorlatinib. A literature review was performed to identify all previously reported pregnancies of ALK+ NSCLC. The collection, determination, and analysis of lorlatinib pharmacokinetics and mass spectroscopy imaging of lorlatinib are both performed.

RESULTS: A 33-year-old pregnant woman with a 7-year history of ALK+ metastatic NSCLC was admitted to the hospital with brain metastases recurrence at 20 weeks of gestation. She self-discontinued lorlatinib at 4 weeks of gestation after long-term disease control on a reduced dose. According to the patient's preference, low-dose lorlatinib was reintroduced at 20 weeks, with successful tumor control and normal fetal growth. At 20-month follow-up postpartum, the mother maintained intracranial and systemic remission, and no congenital abnormalities were observed in the baby. Pharmacokinetic analyses and mass spectroscopy imaging peridelivery confirmed the placental transfer of lorlatinib.

CONCLUSIONS: The case highlights both the potential safety and safety concerns with the use of lorlatinib during pregnancy, along with the unique nature of central nervous system-dominant ALK+ NSCLC, and the potential clinical utility of dose-reduced lorlatinib.