Antibody-drug conjugates (ADCs) have become an increasingly important part of treatment for several advanced cancers, pairing a tumor-targeting antibody with a cytotoxic payload. Their growing use has also brought greater attention to treatment-related toxicities that can affect patients’ quality of life and their ability to remain on therapy. New research suggests that oral complications deserve particular attention.

A multicenter retrospective cohort study published in The Oncologist evaluated oral toxicities among 207 patients with advanced cancer treated with TROP2- or HER2-directed ADCs. Alessandro Villa, D.D.S., Ph.D., M.P.H., chief of Oral Medicine, Oral Oncology and Dentistry at Baptist Health Herbert Wertheim Cancer Institute, was senior author of the study, which included patients treated at Baptist Health and Sapienza University Hospital in Rome.

Overall, 22.7 percent of patients developed at least one oral toxicity. The investigators documented several types of complications, including oral mucositis and xerostomia. They also observed dysgeusia and oral dysesthesia, a burning or otherwise abnormal oral sensation that the authors report has not previously been described in association with ADC therapy.

“Oral toxicities can be easy to underestimate, particularly when patients are dealing with the broader demands of advanced cancer treatment,” Dr. Villa says. “Pain or ulceration can interfere with eating, while dry mouth and taste changes can further affect a patient’s daily life. In some cases, these toxicities can also influence how cancer treatment is delivered.”

The pattern of toxicity differed according to the type of ADC. Oral mucositis occurred in 14.8 percent of patients receiving TROP2-directed therapy compared with 5.4 percent of those receiving HER2-directed therapy. After adjustment, patients receiving a TROP2-directed ADC had approximately three times the odds of developing mucositis.

The lesions most often involved the tongue and were frequently painful. TROP2-associated mucositis also tended to appear earlier than mucositis associated with HER2-directed treatment. Patients in the TROP2 group were more likely to require supportive treatment for oral complications, and dose reductions were also more common, occurring in 26.1 percent of patients compared with 14.1 percent of those receiving HER2-directed therapy. Xerostomia and dysgeusia, meanwhile, were more common among patients receiving HER2-directed therapy, although the differences were not statistically significant.

One of the study’s most clinically relevant findings involved the management of mucositis. Topical corticosteroids are sometimes used for ADC-associated mucositis, in part because they have been effective for stomatitis associated with mTOR inhibitors. In this cohort, however, topical corticosteroids did not improve existing mucositis or prevent new lesions.

“This is an important reminder that oral toxicities associated with different anticancer therapies may not share the same biology,” Dr. Villa says. “We should be cautious about applying a supportive-care strategy from one drug class to another without evidence that it provides the same benefit.”

Oral cryotherapy appeared more promising, although the number of patients who received it was small. Among four patients treated with cryotherapy, the investigators observed symptomatic improvement as well as fewer new ulcerative lesions. Dose modification also contributed to improvement in some patients. These observations will need to be tested in prospective studies before firm treatment recommendations can be made.

For physicians, the findings underscore the importance of asking patients specifically about oral symptoms. Patients may not mention dry mouth or changes in taste during an oncology visit, particularly when other treatment-related effects seem more urgent. Mild oral discomfort can also progress before it becomes apparent during a routine examination.

A baseline oral assessment before ADC therapy may help identify existing problems that could complicate treatment. Once therapy begins, regular discussion of oral symptoms and timely examination of new lesions can help identify toxicity earlier. Referral to an oral medicine specialist should also be considered when symptoms are persistent, painful, or difficult to manage.

The investigators note several limitations. The study was retrospective, and most participants had breast cancer, which limits how broadly the results can be generalized. Oral toxicities may also have been underreported because the researchers relied on medical records rather than standardized prospective oral examinations.

Even with those limitations, the study provides useful real-world evidence as ADC use continues to expand across oncology. Better recognition of oral toxicities, combined with prospective research into prevention and treatment, could help clinicians manage these complications more effectively while supporting patients throughout cancer therapy.

For more information on Dr. Villa’s research and open trials, please visit here.