Oral adverse events in cancer patients treated with VEGFR-directed multitargeted tyrosine kinase inhibitors

Objectives: This study characterized the incidence and clinical features of oral adverse events among cancer patients who received VEGFR-directed multitargeted tyrosine kinase inhibitor (VR-TKI) therapies.

Methods: Electronic medical records of adult cancer patients treated with sunitinib, sorafenib, regorafenib, pazopanib, cabozantinib, imatinib, and bevacizumab therapy at Dana-Farber Cancer Institute from 2009 to 2012 were reviewed. Data collected included patient characteristics, oral and non-oral adverse events, and time to onset. Time oral adverse event-free was the primary outcome.

Results: A total of 747 patients with 806 individual courses of therapy were treated for a median of 3.9months with sunitinib (n=161), sorafenib (n=172), regorafenib (n=15), pazopanib (n=132), cabozantinib (n=23), imatinib (n=144), or bevacizumab (n=159) for lung cancer (21%), gastrointestinal stromal tumor (15%), and metastatic renal cell carcinoma (13%). An oral adverse event was reported in 23.7% of patients at a median of 1.9months after starting therapy. The most commonly reported oral adverse event was oral mucosal sensitivity (dysesthesia), occurring in 12% of patients, typically without clinical findings. Multivariate models showed patients who received VR-TKI therapy were at greater risk of any oral adverse event compared with patients treated with imatinib or bevacizumab. Patients receiving VR-TKI therapy who developed an oral adverse event were also at increased risk for hand-foot skin reaction (15.9%).

Conclusions: VR-TKI associated oral adverse events are characterized primarily by dysesthesia with lack of clinical signs. Oral dysesthesia is more commonly associated with VR-TKIs than with bevacizumab or imatinib. Management is largely empirical and requires further investigation.