Treatments During Pregnancy Targeting ERBB2 and Outcomes of Pregnant Individuals and Newborns

Abstract

ImportanceTargeted therapies directed against ERBB2 are the cornerstone of medical treatment for ERBB2-positive breast cancers but are contraindicated during pregnancy.ObjectivesTo describe the association of exposure to anti-ERBB2 agents during pregnancy with pregnancy and fetal or newborn outcomes, and to compare the risk and types of adverse outcomes reported more frequently in this context than after exposure to other anticancer agents.Design, Setting, and ParticipantsFor this case-control study, All reports with a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. All reports with a pregnancy, an antineoplastic treatment during pregnancy, and a cancer were retained. Reports with anticancer agents prescribed for nononcologic purposes were not included.ExposureThe exposure group was defined as reports that mention anti-ERBB2 agents compared with exposure to other anticancer agents.Main Outcome and MeasuresThe main outcome was the reporting odds ratio (ROR) for maternofetal complications in the group exposed to anti-ERBB2 agents compared with other anticancer agents, as determined using a disproportionality analysis.ResultsA total of 3558 reports (anti-ERBB2 agents, 328; other anticancer agents, 3230) were included in the analysis. In the group exposed to anti-ERBB2 agents, most reports were from the US (159 [48.5%]), the mean (SD) age of participants was 30.8 (10.4) years, and 209 patients (97.7%) were treated for breast cancers. The molecules most frequently involved in cases with anti-ERBB2 agents were trastuzumab (n = 302), pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18). The outcomes overreported in these cases included oligohydramnios (ROR, 17.68 [95% CI, 12.26-25.52]; P < .001), congenital respiratory tract disorders (ROR, 9.98 [95% CI, 2.88-34.67]; P < .001), and neonatal kidney failure (ROR, 9.15 [95% CI, 4.62-18.12]; P < .001). Sensitivity and multivariable analyses found similar results. Toxic effects were also significantly overreported for trastuzumab-emtansine (cardiovascular malformation: ROR, 4.46 [95% CI, 1.02-19.52]) and lapatinib (intrauterine growth restriction: ROR, 7.68 [95% CI, 3.01-19.59]).Conclusions and RelevanceIn this case-control study of 328 individuals exposed to anti-ERBB2 agents during pregnancy, exposure was associated with a severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments.

Immune Checkpoint Inhibitor Use During Pregnancy and Outcomes in Pregnant Individuals and Newborns

“…We found that individuals exposed to anti- ERBB2 drugs during pregnancy were at higher risk of oligohydramnios (ROR, 17.68; 95% CI, 12.26-25.52; P < .001), fetal or neonatal kidney failure (ROR, 9.15; 95% CI, 4.62-18.12; P < .001), and congenital respiratory malformations (ROR, 9.98; 95% CI, 2.88-34.67; P = .001), in line with previously published evidence, thus validating the use of VigiBase as a useful resource to investigate the association of pregnancy, fetal, and/or newborn outcomes with anticancer drugs. This study gave evidence for the risk of oligohydramnios provoked by fetal kidney insufficiency that could, in some rare cases, lead to respiratory tract malformations …”

“…In previous research using VigiBase, some of us performed a case-control disproportionality analysis to determine the reporting odds ratio (ROR) of pregnancy and/or fetal or newborn outcomes associated with exposure to anti- ERBB2 drugs compared with exposure to other anticancer drugs. 19 We found that individuals exposed to anti- ERBB2 drugs during pregnancy were at higher risk of oligohydramnios (ROR, 17.68; 95% CI, 12.26-25.52; P < .001), fetal or neonatal kidney failure (ROR, 9.15; 95% CI, 4.62-18.12; P < .001), and congenital respiratory malformations (ROR, 9.98; 95% CI, 2.88-34.67; P = .001), in line with previously published evidence, 20 , 21 thus validating the use of VigiBase as a useful resource to investigate the association of pregnancy, fetal, and/or newborn outcomes with anticancer drugs. This study gave evidence for the risk of oligohydramnios provoked by fetal kidney insufficiency that could, in some rare cases, lead to respiratory tract malformations.…”

“…This study gave evidence for the risk of oligohydramnios provoked by fetal kidney insufficiency that could, in some rare cases, lead to respiratory tract malformations. 19 …”

Caring for Pregnant Patients with Cancer: A Framework for Ethical and Patient-Centred Care

“…On the contrary, other reports present positive maternal outcomes after immunotherapy exposure [13][14][15]. Further reviews also suggest that targeted therapies (e.g., trastuzumab) in the first trimester are less likely to lead to complications [16], and their use during pregnancy might be possible under close monitoring [17], but the risk of pregnancy and foetal complications remains high [18]. Thus, standard treatments cannot be always given to pregnant cancer patients, reinforcing the difficulty of managing such patients.…”