Brief Report: Alectinib With Salvage Platinum-Taxane Chemotherapy in a Pregnant Woman With ALK-Rearranged NSCLC and Rapid Disease Progression Followed by a Successful Pregnancy.

INTRODUCTION: ALK-rearranged NSCLC is a distinct molecular subtype that disproportionally affects younger never-smoking females, which overlaps with the reproductive age group. Alectinib is a second-generation ALK inhibitor and is generally considered a safer option during pregnancy compared with lorlatinib. Here, we describe a case of a patient who became pregnant while on alectinib complicated by rapid disease progression, with a focus on maternal-fetal outcomes and placental health.

METHODS: A brief report was conducted detailing clinical management by a multidisciplinary team, pharmacokinetic analysis of alectinib levels, and post-delivery placental examination, including histopathology and mitochondrial respirometry function assessment as an indicator of placental health.

RESULTS: A 29-year-old woman with metastatic ALK-rearranged NSCLC became pregnant while on alectinib therapy. At 24 weeks of gestation, she experienced rapid systemic disease progression manifesting as marantic endocarditis with multi-territory small cerebral infarcts, thrombocytopenia, an elevated D-dimer level, and development of two large middle cerebral ischemic strokes requiring endovascular clot retrieval. Carboplatin and paclitaxel chemotherapy was added to alectinib. The patient responded well to the treatment and successfully delivered an infant through elective caesarean section at 34+5 weeks. The patient was switched to lorlatinib plus pemetrexed postpartum. Although she achieved a complete metabolic response with lorlatinib plus pemetrexed, disease progression occurred after several months, and she died 28 months after initial diagnosis. Placental analysis revealed features indicative of fetal growth restriction. Mitochondrial function appeared within normal limits, despite changes in placental morphology. The infant has shown normal development at 9 months of age.

CONCLUSIONS: This is the first reported case of concurrent alectinib and cytotoxic chemotherapy during pregnancy, successfully used in the setting of progressive ALK-rearranged NSCLC. The placental findings align with observations in pregnancies complicated by fetal growth restriction. This case highlights the potential feasibility and safety of intensification of systemic therapy during pregnancy and underscores the importance of individualized multidisciplinary care.