Abstract OT3-1-07: MotHER: A US registry for women with breast cancer who have received trastuzumab, pertuzumab in combination with trastuzumab, or trastuzumab emtansine (T-DM1) during pregnancy or within 7 months prior to conception

Abstract

Abstract Background: Trastuzumab (Herceptin) and pertuzumab (Perjeta) are HER2-targeted monoclonal antibodies, and T-DM1 (Kadcyla) is a HER2-targeted antibody–drug conjugate. These molecules are classified as FDA Pregnancy Category D, indicating evidence of fetal harm; there have been postmarketing reports of oligohydramnios in women who received trastuzumab during pregnancy; in non-clinical studies of pertuzumab, oligohydramnios, delayed renal development, and embryo-fetal death occurred in pregnant cynomolgus monkeys. Furthermore, maytansine, the parent molecule of DM1, has demonstrated embryotoxicity in mice. The MotHER pregnancy registry was established in 2008 as an FDA postmarketing commitment to evaluate the effects of trastuzumab on pregnancy outcome. Pertuzumab and T-DM1 were included in the registry following their respective FDA approvals in 2012 and 2013. Study design: MotHER is a US pregnancy registry and uses a prospective, observational cohort design. Enrollment is voluntary and can be initiated by the patient or her healthcare provider. Women are followed up until pregnancy outcome; infants are followed up through the first year of life. Eligibility criteria: Pregnant women ≥18 years of age and resident in the US are eligible if they have received at least one dose of trastuzumab, pertuzumab in combination with trastuzumab, or T-DM1 for breast cancer during pregnancy or within 7 months prior to conception. Enrollment must be initiated before pregnancy outcome is known. Specific aims: The primary outcome measures are pregnancy outcomes and the incidence of pregnancy complications, such as oligohydramnios, congenital anomalies, and fetal/infant functional deficits. Information on potential birth defects, noted either at birth or during pediatric follow-up, is evaluated and classified by a birth defect evaluator/clinical geneticist. Statistical methods: The study is descriptive and not designed for formal hypothesis testing; event rates with 95% confidence intervals will be calculated. Accrual: There is no pre-specified sample size. Data collection is ongoing, from 2009 to 2019 for trastuzumab, from 2012 to 2022 for pertuzumab plus trastuzumab, and from 2013 to 2023 for T-DM1. Fourteen women have enrolled as of January 31, 2014. Citation Format: Vikki Brown, Richard K Miller, Laura Chu, Cheryl Chow, Caroline Trudeau, Elizabeth B Andrews. MotHER: A US registry for women with breast cancer who have received trastuzumab, pertuzumab in combination with trastuzumab, or trastuzumab emtansine (T-DM1) during pregnancy or within 7 months prior to conception [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-1-07.