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Gastrointestinal Toxicity: Are All Antibody-Drug Conjugates Created Equal in Breast Cancer?

By: Amy MacDonald, MS
Posted: Monday, July 8, 2024

Martina Buffoni, MD, of ASST Spedali Civili, Brescia, Italy, and colleagues conducted an extensive literature review to compare the gastrointestinal toxicity profiles of three commonly used antibody-drug conjugates in metastatic breast cancer: ado-trastuzumab emtansine (T-DM1), sacituzumab govitecan-hziy, and fam-trastuzumab deruxtecan-nxki (T-DXd). Their analysis, published in Clinical Breast Cancer, revealed that T-DM1 seemed to be associated with a markedly reduced incidence of gastrointestinal adverse events compared with the other agents.

“Overall, our pooled analysis confirms that trastuzumab emtansine, the first antibody-drug conjugate approved for solid tumors, was well tolerated and its related toxicities were easy to handle. The prevalence of gastrointestinal toxicities, however, was significantly higher with newer antibody-drug conjugates,” Dr. Buffoni stated.

Online data were gathered for all available phase II and III metastatic breast cancer trials for which the three antibody-drug conjugates previously mentioned were used and gastrointestinal adverse events were reported. Overall, 14 studies comprising 5,608 patients with breast cancer were analyzed.

The evaluated gastrointestinal adverse events were nausea, vomiting, diarrhea, constipation, and abdominal pain. A significantly higher frequency of nausea of any grade (65.6% with sacituzumab govitecan, 75% with T-DXd), vomiting of any grade (43.7% with sacituzumab govitecan, 45% with T-DXd), and diarrhea of any grade (59.7% with sacituzumab govitecan, 29% with T-DXd) was recorded as compared with T-DM1.

The authors concluded that awareness of the gastrointestinal adverse event profiles of these three medications and advanced planning for such toxicities may allow patients to maintain adherence to treatment protocols and benefit their quality of life. “In addition to the design and conduction of phase IV studies,” they concluded, “we advocate the collection of new real-life data regarding the safety of these drugs, how side effects are managed, and the efficacy of the supportive measures adopted in the routine clinical practice.”

Disclosure: The study authors reported no conflicts of interest.


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