Introduction

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate the prevalence of oral toxicities including xerostomia, mucositis/stomatitis, dysgeusia, dysphagia, oral/oropharyngeal pain, oral infections, angular cheilitis, osteonecrosis, osteomyelitis, and oral mucosal reactions with ICIs.

Methods

A review protocol was registered with PROSPERO (ID: CRD42023391674). A systematic search of ClinicalTrials.gov was conducted as of April 10, 2022. Studies were selected, assessed, and data extracted using PRISMA guidelines. Oral toxicity data were extracted from study arms using a single immunotherapy drug. Meta-analyses were conducted to summarize prevalence of oral toxicities using random-effects models.

Results

Of 750 screened records, 95 trials were included in the meta-analysis with published results. Time between study completion and first publication on ClinicalTrials.gov was 1 to 146 months (mean = 20.3, SD = 18.4). Weighted pooled prevalence was 5% (95% CI: 4–6%) for xerostomia, 3% (95% CI: 3–4%) for mucositis/stomatitis, 3% (95% CI: 2–3%) for dysgeusia, 2% (95% CI: 1–2%) for dysphagia, 3% (95% CI: 2–4%) for oropharyngeal/oral pain, 2% (95% CI: 1–3%) for oral candidiasis, and 2% (95% CI: 0–4%) for angular cheilitis. Subgroup differences based on ICI drugs were minimal. No trials reported lichenoid or pemphigoid mucosal reactions.

Discussion

Meta-analysis results revealed low prevalence of oral toxicities with ICIs; however, data reporting was limited and inconsistent. Limitations of study dataset reveal a significant need for systematic collection of oral morbidity data as well as improved consistency and compliance of reporting results on ClinicalTrials.gov.

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Author notes

Source of Support: The salary for Graciela M. Nogueras-Gonzalez is partly supported by the Cancer Center Support Grant (National Cancer Institute Grant P30 CA016672).

Competing Interests

Conflict of Interest: None

This work is published under a CC-BY-NC-ND 4.0 International License.

Supplementary data