Avoid anti-HER2 cancer therapies during pregnancy

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.

A version of this article appeared on Medscape.com.