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Basic Science

Poster Session 1

(119) Transplacental transfer of alectinib and osimertinib using an ex vivo human placental perfusion model

Tuesday, February 13, 2024
10:30 AM – 12:00 PM  
Location: Prince George's Exhibit Hall CDE, Lower Atrium Level
Objective: Non-small cell lung cancer is a rare diagnosis in pregnant women but its incidence is increasing during pregnancy. Recent protein kinase inhibitors have improved the prognosis of specific molecular subtypes (epidermal growth factor receptor-mutant and anaplastic lymphoma kinase-rearranged), but little is known about their use during pregnancy. Thus, we aimed to determine transplacental transfer and cotyledon accumulation of osimertinib and alectinib, using the human perfused placental cotyledon model.

Study Design: Human term placentas from normal pregnancies were collected after delivery and were perfused with osimertinib or alectinib associated with its principal active metabolite M4 at targeted maternal concentrations. We evaluated transport parameters such as fetal transfer rate (FTR) and clearance index (CI), as well as cotyledon accumulation. Antipyrine was used as a control marker. Samples were collected during a 90 minute-procedure.

Results: Mean FTR and mean CI of osimertinib were 9.5% and 0.42, respectively. Mean osimertinib cotyledon accumulation index was 28.9 % i.e. 116,7 µg/100 mg. Conversely, nor alectinib neither M4 were detected in fetal samples. However, mean alectinib cotyledon accumulation index was 370.7 % i.e., 574 µg/100 mg and mean M4 cotyledon accumulation index was 178.5 % i.e. 79.3 µg/100 mg.

Conclusion: Our results suggest that osimertinib significantly crosses the placenta with a moderate placental uptake. Conversely, alectinib and its metabolite M4 do not cross the placental barrier and massively accumulate in placental tissue.