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

• VR-TKI oral adverse events are characterized by dysesthesia with lack of clinical signs.
• Oral dysesthesia is more common with VR-TKIs than with bevacizumab or imatinib.
• Patients with a VR-TKI oral adverse event had increased risk for hand-foot skin reaction.
• Management is largely empirical and requires further investigation.

SummaryObjectivesThis 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.MethodsElectronic 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.ResultsA total of 747 patients with 806 individual courses of therapy were treated for a median of 3.9 months 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 1.9 months 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%).ConclusionsVR-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.