Genotype-directed therapy for non-small cell lung cancer diagnosed during pregnancy: A pooled analysis of seven cases from the Cancer and Pregnancy Registry with maternal and neonatal outcomes and review of the literature.

introductionPregnant patients with cancer are routinely excluded from the clinical trials, limiting the evidence to guide the management of advanced malignancies during pregnancy. Data regarding maternal and neonatal outcomes associated with genotype-directed therapy for non-small cell lung cancer (NSCLC) during pregnancy remain limited. MATERIAL AND

methodsWe conducted a retrospective multicenter, pooled analysis of pregnant patients diagnosed with NSCLC between 2002 and 2024 who were enrolled in the Cancer and Pregnancy Registry (ClinicalTrials.gov identifier: NCT02749474). Consecutive cases diagnosed during pregnancy were included. Clinical presentation, tumor histology and stage, biomarker and molecular profiling, oncologic treatment administered during pregnancy, obstetric management, maternal outcomes, and neonatal outcomes including pediatric developmental follow-up were systematically reviewed and analyzed.

resultsSeven pregnant patients were diagnosed with NSCLC at a median gestational age of 22.4 weeks (range, 10.4-28.8 weeks). Five patients presented with stage IV disease, one with stage III disease, and one with stage II disease. Biomarker testing identified actionable alterations in all 6 patients who underwent testing, including epidermal growth factor receptor (EGFR) mutations or amplification (n = 4), anaplastic lymphoma kinase (ALK) rearrangement (n = 1), and ROS1 rearrangement (n = 1). Biomarker-directed therapy, including osimertinib or alectinib, was administered during the second or third trimester in 3 patients. All pregnancies resulted in live births, including one dichorionic diamniotic twin gestation, yielding eight infants. Median gestational age at delivery was 34.9 weeks. Five infants were small for gestational age, and two required early intervention for prematurity-related developmental delays. No congenital anomalies or placental metastases were observed. Four patients remained alive and clinically stable at least 2.3 years after diagnosis, while all mothers survived to or beyond their child's first birthday.

conclusionsIn this limited retrospective study, biomarker-directed therapy during pregnancy was associated with maternal disease control and continuation of pregnancy into later gestation in selected patients. No major fetal toxicity signal was identified; however, these findings should not be interpreted as establishing the safety of targeted therapy during pregnancy. Early biomarker testing and individualized multidisciplinary management may help inform treatment decision-making for carefully selected patients with NSCLC diagnosed during pregnancy.