A survey study of prevention and treatment patterns by academic and community oncologists for hand-foot skin reaction associated with vascular endothelial growth factor receptor inhibitor (VEGFRi) therapy.
Authors: Lacouture Mario E. , Anadkat Milan J. , Patel Anisha B , Marathe Omkar Subhash , Webb Mark L , Tyler Robert Claude , Chen Liping , Wu Chengguang , Li Wenxi , Ju Juegang , Luo Jie , Tang Hong , Vogelzang Nicholas J. 
Published: February 2022

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Background: VEGFRi therapies are associated with hand-foot skin reaction (HFSR) that affects up to 69% of patients depending on the VEGFRi administered. The incidence and severity of HFSR are dose-dependent and have been associated with improved clinical outcomes suggesting a direct toxicity mechanism. HFSR significantly diminishes patients’ quality of life and effects optimal treatment. Current HFSR treatments focus on managing symptoms since there are no effective therapies that address the underlying cause of HFSR. Small studies and expert opinion have suggested treating HFSR with topical corticosteroids or urea-based creams. However, the most effective management remains dose reduction/interruption or treatment discontinuation. This survey was conducted to assess current toxicity management patterns and treatment gaps for VEGFRi associated HFSR. Methods: An online survey (MedSurvey) with 5 eligibility & 8 questions related to VEGFRi practice patterns was conducted (April 27 to 30, 2021). Fifty-one (51) practicing oncologists completed the survey. Results: Among the 51 oncologists, 86% have been practicing ≥ 11 yrs with 37% from an academic setting and 63% from a community setting. They (percent of respondents) prescribed cytotoxic chemotherapy (91%) and targeted agents (84%) more than 10 times per week. Prevention of VEGFRi-induced HFSR with urea (57%) or topical steroids (75%) were the commonly administered prophylactic treatments. The majority (53%) would prophylactically use a novel agent to prevent HFSR, while 33% would use it for HFSR prevention in a patient with a previous occurrence, and 12% would use this agent for selected VEGFR inhibitors. Many oncologists (4% always, 61% sometime/frequently) start a VEGFRi at a lower dose and titrate up to prevent HFSR. For grade 1 HFSR (multiple choices allowed), 37% used observation only for management, whereas 51% prescribed urea ointment, and 63% used a topical steroid. Dose reduction was implemented 20% of the time. For grade 2 HFSR (multiple choices allowed) 53% used urea ointment, 84% prescribed a topical steroid and 59% considered dose reduction as a treatment strategy. For patients not responding to standard therapy 2% switched to a different anti-cancer regimen, 18% changed the VEGFRi, while 78% interrupted the VEGFRi therapy. Conclusions: Treating VEGFRi-associated HFSR continues to be a significant challenge with grade 2/3 toxicity or patients not responding to standard treatment. This often requires a therapeutic dose reduction or interruption that may impact the efficacy of anti-cancer treatment. Effective management (prevention and treatment) for skin toxicities associated with targeted-multikinase/VEGFRi inhibitors remains an unmet need for many patients and a treatment challenge for oncologists.