OT1-02-11: MotHER: A Registry Developed for Women with Breast Cancer Who Have Received Trastuzumab within 6 Months Prior to Conception or during Pregnancy.

Abstract

Abstract Background: Trastuzumab is a humanized monoclonal antibody that targets HER2, a protein that is overexpressed in approximately 20% of patients with breast cancer (BC). Trastuzumab is approved for the treatment of HER2−positive BC in both the metastatic and adjuvant settings, and is classified as US Food and Drug Administration (FDA) Pregnancy Category D, which indicates evidence of fetal harm, but benefit may outweigh risk. In the postmarketing setting, oligohydramnios has been reported in patients who received trastuzumab during pregnancy either alone, or in combination with chemotherapy. As a result, this registry was requested by the FDA and was established as part of a post-marketing commitment. Study Design: MotHER uses a prospective, observational cohort design to evaluate the outcomes of pregnancies in women exposed to trastuzumab within 6 months prior to conception or during pregnancy. Women are followed until pregnancy outcome is known; infants are followed through the first year of life. Medical information is primarily collected from the patient's healthcare providers (HCPs) (ob/gyn, oncologist, pediatrician). Using a standardized recording and coding system, information collected on potential defects noted at birth or during the pediatric follow-up period is evaluated and classified by a birth defect evaluator/clinical geneticist. Eligibility Criteria: Enrollment is voluntary and must be initiated by the patient before the pregnancy outcome. Enrollment may be suggested by an HCP. A verbal informed consent process is used. Patients with known prenatal testing results may enroll; however, to reduce the potential for bias, patients with knowledge of prenatal testing results (either normal or abnormal) will be analyzed as a separate subset. Aims: The aim of this study is to evaluate the effects of trastuzumab therapy on pregnancy outcome in women who were administered trastuzumab while pregnant. The MotHER registry is the first prospective cohort study to be established for investigating the effects of a targeted cancer therapy on pregnancy outcome. The greatest challenge for this registry is to enroll a sufficient number of patients from the relatively small population of trastuzumab-exposed women who become pregnant. Analysis Methods: Primary outcome measures are the occurrences of oligohydramnios, live births, fetal deaths/stillbirths (≥20 weeks gestation), and fetal/infant major malformations, deformations, disruptions or functional deficits. Secondary outcomes include pre-term births, elective terminations, miscarriages, fetal growth abnormalities, and pregnancy or delivery complications. The sample size has not been pre-specified. The study is descriptive: event proportions and associated confidence intervals will be calculated; statistical testing is inappropriate. Accrual: This registry was activated in December 2008 and will accrue in the US over a 10-year period. As of June 20, 2011, 5 patients had been enrolled. Contact Information: Patient and HCP awareness of the registry and willingness to participate are crucial to its ultimate success. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-11.