Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors

Abstract

Development of biological targeted therapies and immune checkpoint inhibitors has redefined the treatment for many cancers; however, the increasing use of new protocols has led to physicians observing a new spectrum of toxicities. To date, oral adverse events induced by these new anticancer therapies have been mainly reported using nonspecific terminology (Bstomatitis,^Bmucosal inflammation,^Bmucositis^) and remain poorly characterized, with the exception of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis. Oral toxicities of targeted therapies often display very characteristic features which clearly differ from classic oral injuries observed with cytotoxic chemotherapy and/or radiotherapy. In addition, they frequently affect more than 20% of treated patients and can lead to a significant morbidity or permanent treatment discontinuation. Oral mucosal toxicities described in this review include mTOR inhibitor-associated stomatitis (mIAS); stomatitis, benign migratory glossitis, and osteonecrosis of the jaw associated with multi-targeted kinase inhibitors of the VEGF and PDGF receptors; mucositis induced by EGFR inhibitors (in monotherapy or in combination with head and neck radiotherapy and/or chemotherapy); hyperkeratotic lesions with BRAF inhibitors; pigmentary changes and lichenoid reactions secondary to imatinib; and more recent data on the BOsler-Weber-Rendu-like syndrome^described with the antibody-drug conjugate, TDM-1. Finally, we provide, to our knowledge, the first available structured data on oral toxicities induced by the new recently FDA-and EMA-approved monoclonal antibodies targeting PD-1. Clinical management of these targeted therapy-related oral changes is also discussed.

Oral lichenoid reactions associated with anti‐PD‐1/PD‐L1 therapies: clinicopathological findings

“…Regular oral examinations should be offered to treated patients. 10 Finally, a lesional biopsy should be recommended for any persistent or atypical lesions.…”

Dose‐limiting stomatitis associated with ibrutinib therapy: a case series

“…Aphthous‐like lesions on nonkeratinized mucosa have been previously reported with other therapies targeting different kinase pathways, especially mammalian target of rapamycin (mTOR) inhibitors. We also recently characterized similar mucosal involvement with several other tyrosine kinase inhibitors (TKIs) targeting human epidermal growth factor receptor (HER) (HER1‐ erlotinib , gefitinib , pan HER‐ afatinib , dacomitinib ) or with multikinase angiogenesis inhibitors ( sorafenib , sunitinib , pazopanib ) (Vigarios et al , ).…”

“…The clinical presentation of ibrutinib‐associated stomatitis clearly differs from mucositis induced by chemotherapeutic agents, usually starting with distinct ulcerations that ultimately become diffuse, poorly circumscribed and confluent. Moreover, chemo‐induced mucositis appears 4–7 days after the first cycle (Vigarios et al , ) and solely involves nonkeratinized mucosae. Aphthous‐like lesions on nonkeratinized mucosa have been previously reported with other therapies targeting different kinase pathways, especially mammalian target of rapamycin (mTOR) inhibitors.…”

Future trends and emerging issues for nanodelivery systems in oral and oropharyngeal cancer

“…Loading the NPs with a fluorescent dye (rhodamine B) instead of CDDP allowed for the visualization and quantification of successful uptake of the NPs in the oral cancer cells and revealed a significantly higher uptake of the NPs containing the NR7 peptide. 41,60 In in vivo studies, NP-treatment efficiency is assessed by histological examinations of H&E-stained preparations of the sample under light microscopy 61 or through more advanced methods. These include analysis of fluorescent or bioluminescent signals with an in vivo imaging system 62 or Raman spectra differences through Raman spectroscopy.…”