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.