Oral Toxicities With Antibody-Drug Conjugates: What Physicians Should Know

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.

By
October 9, 2026
4 min

Baptist Health South Florida

Overview

In a multicenter retrospective cohort of 207 patients with advanced cancer treated with TROP2- or HER2-directed antibody-drug conjugates (ADCs), 22.7% developed at least one oral toxicity. Mucositis was more frequent and associated with earlier onset and more dose reductions in the TROP2 group, while topical corticosteroids did not improve or prevent mucositis in this cohort.

Background

ADCs combine a tumor-targeting antibody with a cytotoxic payload and are increasingly used to treat advanced cancers. Treatment-related oral complications can affect eating and daily life and, as described by the study’s senior author, may influence how cancer treatment is delivered. The study examined oral toxicities in patients receiving TROP2- or HER2-directed ADCs at two centers. Its retrospective design and reliance on medical records limit generalizability and may have led to underreporting.

Data Highlights

Finding	Result
Patients with at least one oral toxicity	22.7% of 207 patients
Oral mucositis with TROP2-directed ADCs	14.8%
Oral mucositis with HER2-directed ADCs	5.4%
Adjusted odds of mucositis with TROP2-directed ADCs	Approximately three times those with HER2-directed ADCs
Dose reductions, TROP2 versus HER2 group	26.1% versus 14.1%
Patients receiving oral cryotherapy	4; symptomatic improvement and fewer new ulcerative lesions were observed

Key Findings

The cohort included 207 patients with advanced cancer treated with TROP2- or HER2-directed ADCs; 22.7% developed at least one oral toxicity.
Reported complications included oral mucositis, xerostomia, dysgeusia, and oral dysesthesia. The authors described oral dysesthesia as not previously reported in association with ADC therapy.
Mucositis occurred in 14.8% of patients receiving TROP2-directed therapy and 5.4% receiving HER2-directed therapy; adjusted odds were approximately three times higher with TROP2-directed ADCs.
Mucositis associated with TROP2-directed therapy tended to appear earlier; lesions most often involved the tongue and were frequently painful.
Supportive treatment was more often required in the TROP2 group, where dose reductions occurred in 26.1% of patients, compared with 14.1% in the HER2 group.
Xerostomia and dysgeusia were more common with HER2-directed therapy, but differences were not statistically significant. Topical corticosteroids did not improve existing mucositis or prevent new lesions; improvement and fewer new ulcerative lesions were observed among four patients treated with oral cryotherapy.

Clinical Implications

The study authors describe asking specifically about oral symptoms, assessing the mouth before ADC therapy, and examining new lesions during treatment as ways to identify oral toxicity. They also state that referral to an oral medicine specialist should be considered for persistent, painful, or difficult-to-manage symptoms. The observed cryotherapy findings require prospective study before firm treatment recommendations can be made.

Conclusion

This retrospective cohort documents oral toxicities among patients receiving TROP2- and HER2-directed ADCs, with differing patterns between treatment groups. Prospective studies are needed to evaluate prevention and management strategies.