Pregnancy Outcomes in Patients Treated with Bosutinib
Authors: Cortes Jorge E. , Gambacorti-Passerini Carlo , Deininger Michael W. , Abruzzese Elisabetta , DeAnnuntis Liza , Brümmendorf Tim H 
Published: October 2019

Abstract
Introduction: Studies in animals have shown reproductive toxicity with bosutinib exposure, with teratogenic events in maternal exposure, but little is known about its effect during conception or pregnancy in humans.
Methods: Here we describe pregnancy outcomes in bosutinib-treated patients from the Pfizer safety database, which includes cases from both clinical trials and spontaneous reports. Pregnancy cases reported up to February 28, 2018 were identified by searching the database using the Standardized MedDRA Query Pregnancy and Neonatal Topics in patients receiving bosutinib.
Results: The database search identified 33 relevant pregnancy reports, including 17 cases of exposure via the father and 16 cases of maternal exposure. Among the 16 cases of maternal exposure, 5 vaginal deliveries of healthy babies, 2 patient-requested induced abortions, 1 spontaneous abortion, and 1 partial molar pregnancy requiring a dilation and curettage were reported. In 1 case, the patient was reported to have delivered a baby, but the details of the status of the baby was not provided. Outcomes in 6 cases are unknown. Of the healthy deliveries, 4 pregnancies went to full term (≥39 weeks) and 1 was of unknown duration; bosutinib was discontinued during the first trimester of pregnancy in all 5 cases. The reported spontaneous abortion was due to a suspected ectopic pregnancy in a 34-year-old patient who began taking bosutinib 500 mg once daily while pregnant and was thought to be unrelated to bosutinib exposure.
Of the 17 cases of exposure via father, 8 vaginal deliveries of healthy babies, 1 Caesarean section delivery of a healthy baby, 4 induced abortions, and 1 spontaneous abortion were reported. The remaining 3 cases had unknown outcomes. Of the 4 induced abortions, 1 was elective due to an unintended pregnancy, and 2 were due to unknown reasons. In the last case, it was reported that the fetus was not growing properly and that the pregnancy would subsequently be terminated; no confirmation of congenital abnormality or further information is available. The reported spontaneous abortion was thought to be unrelated to bosutinib; fetal biopsy revealed basal deciduitis with necrosis loci and bleeding.
Conclusions: Overall, a review of the available experience with bosutinib in pregnancy did not identify any safety signals. However, adverse effects of bosutinib exposure at conception or during pregnancy in humans cannot be ruled out, particularly if therapy is not interrupted upon recognition of pregnancy. Bosutinib is not recommended for use during pregnancy, and patients on bosutinib treatment should use effective contraception.

Disclosures
Cortes: Astellas Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Arog: Research Funding. Gambacorti-Passerini:BMS: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding. Deininger:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Blueprint: Consultancy. Abruzzese:Novartis: Consultancy; Ariad: Consultancy; BMS: Consultancy; Pfizer: Consultancy. DeAnnuntis:Pfizer Inc: Employment, Equity Ownership. Brümmendorf:Janssen: Consultancy; Merck: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy.