Brief Report: Successful Pregnancy and Healthy Baby Outcome in a TKI-refractory ALK+ NSCLC Patient with CNS Metastasis Treated with Lorlatinib with Maternal-fetal Pharmacokinetics and Child Milestone Development Correlations.

Background: Lorlatinib is the preferred first-line treatment for advanced anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC) based on 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-positive NSCLC who became pregnant during treatment with lorlatinib. A literature review was performed to identify all previously reported pregnancies of ALK-positive 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-positive mNSCLC, 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 patient's preference, low dose lorlatinib was re-introduced at 20 weeks, with successful tumor control and normal fetal growth. At 20-month follow-up post-partum, the mother maintained intracranial and systemic remission and no congenital abnormalities were observed in the baby. Pharmacokinetic analyses and mass spectroscopy imaging peri-delivery confirmed 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 CNS-dominant ALK-positive NSCLC, the potential clinical utility of dose-reduced lorlatinib.