Pharmacokinetic study of erlotinib in a pregnant woman with advanced non‐small cell lung cancer and observation of the effects on the child growth

• Published in: British journal of clinical pharmacology Vol. 90; no. 10; pp. 2554 - 2561
• Main Authors: Aida, Yuka, Ohgami, Masahiro, Mukai, Yuji, Matsuyama, Masashi, Obata‐Yasuoka, Mana, Satoh, Toyomi, Homma, Masato, Sekine, Ikuo, Hizawa, Nobuyuki
• Format: Journal Article
• Language: English
• Published: England 01-10-2024
• Subjects: Adenocarcinoma - drug therapy; Adult; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Child; Child Development - drug effects; ErbB Receptors - genetics; erlotinib; Erlotinib Hydrochloride - administration & dosage; Erlotinib Hydrochloride - adverse effects; Erlotinib Hydrochloride - pharmacokinetics; Erlotinib Hydrochloride - therapeutic use; Female; foetal growth retarded; Humans; Infant, Newborn; Lung Neoplasms - drug therapy; Male; oligohydramnios; OSI‐413; OSI‐420; Pregnancy; Pregnancy Complications, Neoplastic - drug therapy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; pregnant; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - therapeutic use; Quinazolines - administration & dosage; Quinazolines - blood; Quinazolines - pharmacokinetics; Quinazolines - therapeutic use; review; OSI‐420; erlotinib; oligohydramnios; review; OSI‐413; foetal growth retarded; pregnant
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/bcp.16120

Aims
The aim of the study is to report the clinical and pharmacological observations from a pregnant patient treated with erlotinib in the second and third trimesters of pregnancy.
Methods
Maternal and neonatal blood levels and safety of erlotinib and its metabolites were evaluated. Child development was monitored for 6 years.
Results
A 31‐year‐old woman with stage IV lung adenocarcinoma with EGFR exon19 deletion began treatment with erlotinib 150 mg/day at 17 weeks of gestation. Although foetal growth retardation and oligohydramnios were observed at several times during the pregnancy, treatment was continued due to the severity of the maternal presentation, with ongoing foetal monitoring. The foetus seemed to tolerate and recover well without specific interventions. A healthy baby boy was delivered at 37 weeks gestation. The child grew and developed without any obvious issues. At last follow‐up, at age 6 years, he was attending school at a grade appropriate for his age without health or developmental problems. Blood levels of erlotinib were 397–856 ng/mL at 18–37 weeks of gestation and 1190 ng/mL at 8 weeks postpartum. The blood concentration ratios of OSI‐413‐to‐erlotinib ranged from 0.167 to 0.253 at 18–37 weeks of gestation, excluding 24 weeks, and 0.131 at 8 weeks postpartum. The maternal‐to‐foetal transfer rate of erlotinib, OSI‐420 and OSI‐413 were 24.5, 34.8 and 20.3%, respectively.
Conclusion
Erlotinib use during the second and third trimester of pregnancy did not seem to cause any untoward effects on the developing foetus, or any long‐lasting effects that could be detected during 6 years of follow‐up of the child.