Risk Minimization of Antibody-Drug Conjugates in Oncology: A Review.

Antibody-drug conjugates (ADCs) are new treatment options for certain cancers, especially those in advanced states with limited treatment options. Their unique design provides targeted therapy with toxins that otherwise would not be available, but they manifest toxicities that require risk minimization interventions to optimize their tolerability. We summarize selected toxicities for ADCs that have been approved through the end of 2020 and three investigational ADCs, which include both payload and linker, as described in the US Prescribing Information, the European Summary of Product Characteristics, and study protocols. These toxicities include peripheral neuropathy; pulmonary, skin, hepatic, and ocular toxicities; hyperglycemia; left ventricular dysfunction; and fluid-related events. We also review the risk minimization approaches to managing these toxicities as described in the product labels and study protocols. Our general observation suggests that the selected toxicities of the approved ADCs are primarily associated with off-target effects of the drug payloads. We also observed that the risk minimization approaches used to manage the selected toxicities are similar across product labels and study protocols. ADCs provide a unique treatment approach that is currently focused on advanced or refractory cancers. The risk minimization approaches for the selected toxicities for the approved ADCs per product label, or the study protocol for those in clinical investigation, are similar to those of standard chemotherapy agents and other pharmaceutical agents for the treatment of advanced malignancies. These risk minimization measures align with standard medical practice and are likely familiar to and feasible for physicians who prescribe for, and to other healthcare practitioners who care for, patients treated with ADCs.

Pharmacoepidemiologic Evaluation of Birth Defects from Health-Related Postings in Social Media During Pregnancy.

INTRODUCTION: Adverse effects of medications taken during pregnancy are traditionally studied through post-marketing pregnancy registries, which have limitations. Social media data may be an alternative data source for pregnancy surveillance studies. OBJECTIVE: The objective of this study was to assess the feasibility of using social media data as an alternative source for pregnancy surveillance for regulatory decision making. METHODS: We created an automated method to identify Twitter accounts of pregnant women. We identified 196 pregnant women with a mention of a birth defect in relation to their baby and 196 without a mention of a birth defect in relation to their baby. We extracted information on pregnancy and maternal demographics, medication intake and timing, and birth defects. RESULTS: Although often incomplete, we extracted data for the majority of the pregnancies. Among women that reported birth defects, 35% reported taking one or more medications during pregnancy compared with 17% of controls. After accounting for age, race, and place of residence, a higher medication intake was observed in women who reported birth defects. The rate of birth defects in the pregnancy cohort was lower (0.44%) compared with the rate in the general population (3%). CONCLUSIONS: Twitter data capture information on medication intake and birth defects; however, the information obtained cannot replace pregnancy registries at this time. Development of improved methods to automatically extract and annotate social media data may increase their value to support regulatory decision making regarding pregnancy outcomes in women using medications during their pregnancies.