Evidence from Animal Studies
Lurbinectedin, approved as Zepzelca for small cell lung cancer, caused fetal abnormalities in animal reproductive toxicity studies. In rats, intravenous doses at or above 0.3 mg/m² (about 1/10 the human dose on mg/m² basis) during organogenesis led to embryo-fetal lethality, reduced fetal weight, and skeletal variations like incomplete ossification and extra ribs. In rabbits, doses ≥1.2 mg/m² produced similar effects, including post-implantation loss and malformations such as fused sternebrae and retarded ossification.[1][2]
Human Data and Warnings
No adequate human studies exist on lurbinectedin use in pregnancy. The drug's label carries a boxed warning: Zepzelca can cause fetal harm based on its mechanism (DNA damage via trapping topoisomerase I complexes) and animal findings. It is pregnancy category D—positive evidence of human fetal risk from adverse events, but benefits may outweigh risks in life-threatening conditions. Embryofetal toxicity risk is high due to genotoxic potential.[1][2]
Recommendations for Patients
Women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose. Men with partners of childbearing potential should use contraception during treatment and for 4 months post-dose. Discontinue breastfeeding during treatment and for 2 weeks after.[1][2] Providers verify pregnancy status before starting therapy.
Related Clinical Context
Lurbinectedin has not shown teratogenic effects in postmarketing human reports, likely due to its recent approval (2020) and oncology use in advanced patients where pregnancy is rare. Similar DNA-damaging chemotherapies (e.g., topotecan) also carry fetal harm warnings. No published case reports link lurbinectedin directly to human fetal abnormalities as of latest data.[3]
Sources:
[1] Zepzelca (lurbinectedin) prescribing information, Jazz Pharmaceuticals, revised 2023. https://www.zepzelca.com/
[2] FDA Label for Zepzelca, Drugs@FDA database. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213069s000lbl.pdf
[3] PubMed search: "lurbinectedin pregnancy" (no human teratogenicity cases, 0-5 results as of 2024). https://pubmed.ncbi.nlm.nih.gov/?term=lurbinectedin+pregnancy