Metabolic adverse events of multitarget kinase inhibitors: a systematic review

Purpose: Multitargeted kinase inhibitors (MKIs) are used for the treatment of several cancers. By targeting multiple signaling pathways, MKIs have become cornerstones of the oncologic treatment. Although their use leads to important results in terms of survival, treatment with MKIs can determine important side effects the clinician must be aware of. Among those, arterial hypertension, mucositis and skin lesions are universally reported, while data about metabolic alterations are scarce. In our review, we focused on glucose and lipid alterations in MKI-treated patients. Methods: We searched for articles, published between January 2012 and December 2022, evaluating the effects on lipid and glucose metabolism of four MKIs (Cabozantinib, Lenvatinib, Sorafenib, and Vandetanib) in adult patients with cancer. We focused on drugs approved for thyroid malignancies, since a worse metabolic control may potentially impact life expectancy, due to their better overall survival rate. Results: As for glucose metabolism, the majority of the studies reported elevation of glucose levels (prevalence: 1-17%) with different grades of severity, including death. As for cholesterol, 12 studies reported worsening or new-onset hypercholesterolemia (prevalence: 4-40%). Finally, 19 studies reported different grades of hypertriglyceridemia (prevalence: 1-86%), sometimes leading to life-threatening events. Conclusions: Despite some inherent limitations, our analysis may cast light upon some of the MKIs metabolic disorders that can impact on patients’ health, especially when long-term survival is expected. Future clinical trials should consider routine assessment of glucose and lipid levels, because underdetection and underreporting of alterations can lead to the overlooking of important adverse events.