4B-01 - Pregnancy, Lactation, and Fertility Safety Data of FDA-Approved Oncology Therapies: A Systematic Review of Labeling Information (2017–2022)

Background: Cancer incidence continues to rise, particularly among reproductive-aged women, with nearly 1 million female cancer survivors in the US by 2022. Anticancer therapies often receive expedited approvals due to unmet medical needs designation, raising concerns about exceedingly limited pregnancy, lactation, and fertility-related safety data at the time of approval.

Objectives: To describe the available safety information based on a systematical review of pregnancy, lactation, and fertility labeling information for FDA-approved oncology and hematologic malignancy products from Jan 1, 2017, to Oct 31, 2022.

Methods: Using the FDA database, Drugs@FDA, we reviewed approval letters and labels for products treating 8 common cancers in childbearing-age females: breast, cervical, ovarian, skin, and thyroid cancer, multiple myeloma, lymphomas, and leukemia. Using a pre-specified data collection sheet, two reviewers extracted data from (1) label Sections 8.1-8.3 (Pregnancy, Lactation, and Females and Males of Reproductive Potential), (2) post-marketing research, and (3) Risk Evaluation and Mitigation Strategies (REMS) requirements. Source of data (human/animal), requirements for pregnancy testing, contraception, and infertility potential were summarized. Disagreements were resolved by a third reviewer.

Results: Of 81 products (153 labels) reviewed, 32 had original approvals, 33 supplemental approvals, and 16 both. Only 9.9% products had human pregnancy data, 1.2% had human lactation data, 80.3% had animal pregnancy data, and 16.1% had animal lactation data. Post-marketing pregnancy safety monitoring was required for 3 products (1 post-marketing enhanced pharmacovigilance program, 1 pregnancy registry, 1 required both). Lenalidomide, a thalidomide analog, is contraindicated for use in pregnancy with REMS. Safety signals for the other 2 products arose from cases reported in preapproval trials. Pre-initiation pregnancy testing is recommended for 91.4% products. Contraception was advised for 44.4% (both sexes), 49.4% (female only), 2.5% (both sexes and advice against sperm donation), 1.2% (both sexes and sperm donation prohibited). Infertility data was absent for 43.2% of products, 24.7% indicated potential impairment in both sexes, 22.2% in males, 8.6% in females, and 1.2% posed no observed impairment in animals. Label updates included new animal lactation data (1), testing (7), and contraception (4) requirements.

Conclusions: This review highlights the scarcity of human safety data on pregnancy, lactation, and fertility for cancer therapies. Given the increasing number of reproductive-aged cancer survivors, further research is needed to assess reproductive risks associated with cancer treatments.