Tyrosine kinase inhibitor toxicities: A society of gynecologic oncology review and recommendations

Objective. Oral tyrosine kinase inhibitors (TKIs) have new indications for treatment in gynecologic malignan-cies. These targeted drugs have both unique and overlapping toxicities, which require careful attention and man-agement. New combination therapies with immune-oncology agents have demonstrated promise in endometrial cancer. This review examines common adverse events associated with TKIs and provides readers with an evidence-based review on current uses and strategies for the management of these medications.Methods. A comprehensive review of the medical literature on TKI use in gynecologic cancer was undertaken by a committee approach. Details of each drug, its molecular target, and relevant data on both clinical efficacy and side effects were compiled and organized for clinical use. Information on drug-related secondary effects and management strategies for specific toxicities, including dose reduction and concomitant medications, were gathered.Results. TKIs can potentially offer improved response rates and durable responses for a group of patients who were previously without an effective standard second-line therapy. The combination of lenvatinib and pembro-lizumab represents a more targeted approach to the drivers of endometrial cancer; however, there remains significant drug-related toxicity, and thus dose reduction and dose delay are frequently required. Toxicity man-agement requires frequent check-ins and management strategies to help patients find the highest tolerable dose. TKIs are expensive and patient financial toxicity is as critical a measure of a drug's utility as any drug side effect. Many of these drugs have patient assistance programs, which should be fully utilized to minimize cost. Conclusions. Future studies are needed to expand the role of TKIs into new molecularly driven groups. Attention to cost, durability of response, and long-term toxicity management is needed to ensure all eligible patients have access to treatment.(c) 2023 Published by Elsevier Inc.

Automated summary

This article reviews the applications of oral tyrosine kinase inhibitors (TKIs) in gynecologic malignancies and summarizes the common adverse events associated with these drugs and their management strategies. TKIs have the potential to improve response rates and provide durable responses in certain patients. However, drug-related toxicity requires careful attention and management.