Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population.
TPS658 Background: T and P are monoclonal antibodies that target different HER2 epitopes. T is approved for treatment of early and metastatic HER2+ BC while P is approved in combination with T for previously untreated HER2+ MBC. Oligohydramnios has been reported in patients (pts) who received T during pregnancy, and also in P-treated pregnant monkeys. Although both antibodies are FDA Pregnancy Category D, indicating evidence of fetal harm, some physicians and pts accept this risk and continue treatment. The MotHER registry was established in 2008 as an FDA postmarketing commitment to evaluate the effects of T therapy on pregnancy outcome; P was included in the study following its approval in 2012. MotHER is the first prospective study of the effects of a targeted cancer therapy on pregnancy outcome. Methods: MotHER is a US registry study of women exposed to T±P during pregnancy or within 6 months prior to conception. Women enroll voluntarily and are followed until pregnancy outcome; infants are followed through the first year of life. Medical information is primarily collected from healthcare providers. Information on potential birth defects noted at birth or during the pediatric follow-up is classified by a birth defect evaluator/clinical geneticist. Enrollment must be initiated before pregnancy outcome. Pts with known prenatal testing results may enroll, but to reduce the potential for bias these pts will be analyzed as a subset. Primary outcomes: number and nature of pregnancy complications, including oligohydramnios, pregnancy outcomes, fetal/infant outcomes and fetal/infant functional deficits. Secondary outcomes: preterm births, elective/therapeutic abortions, miscarriages, fetal growth abnormalities and delivery complications. The study is descriptive and not for formal hypothesis testing; event proportions with CIs will be calculated. The registry will accrue in the US from 2009 to 2019 for T-treated pts and from 2012 to 2022 for P+T-treated pts. The number of potential pts is small therefore physicians are encouraged to refer any eligible pt to increase knowledge about the safety of T±P in pregnancy. herceptinpregnancyregistry.com. Clinical trial information: NCT00833963.
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.
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