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Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with
Risako Kohya1, Goki Suda1, Masatsugu Ohara1
1Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8648, Japan.
Abstract:
Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates appetite and is involved in cachexia. We evaluated the association between FGF21 level changes during lenvatinib treatment for unresectable HCC and appetite loss. Sixty-three eligible unresectable HCC patients who started lenvatinib treatment between 2018 and 2021 were included. We analyzed FGF21 levels at baseline; 1, 2, and 4 weeks after lenvatinib initiation, and before the onset of appetite loss. Grade ≥ 2 lenvatinib-induced appetite loss led to liver functional reserve deterioration at disease progression and a poor prognosis. Baseline characteristics and serum FGF21 levels were similar between patients with and without appetite loss. However, the serum FGF21 change rate increased significantly at 4 weeks post-lenvatinib initiation in patients with grade ≥ 2 appetite loss, as compared to those without appetite loss. Similar significant increases in the serum FGF21 level change rate were observed prior to grade ≥ 2 appetite loss onset. This suggests that changes in FGF21 levels can be used to predict patients with a greater risk of marked appetite loss and provides insights into the mechanisms underlying lenvatinib-induced appetite loss in patients with HCC.
Insights
Fibroblast growth factor 21 (FGF21) levels increase during lenvatinib treatment for unresectable hepatocellular carcinoma (HCC), predicting significant appetite loss. This finding offers insights into lenvatinib-induced appetite loss mechanisms and patient prognosis.
Area of Science:
- Hepatocellular Carcinoma Research
- Oncology Drug Mechanisms
- Endocrine Signaling in Cancer
Background:
- Lenvatinib is a standard treatment for unresectable hepatocellular carcinoma (HCC).
- Appetite loss is a common side effect of lenvatinib, impacting patient outcomes.
- The mechanisms and predictive factors for lenvatinib-induced appetite loss remain unclear.
Purpose of the Study:
- To investigate the association between changes in serum Fibroblast Growth Factor 21 (FGF21) levels and lenvatinib-induced appetite loss in unresectable HCC patients.
- To explore FGF21 as a potential predictive biomarker for significant appetite loss during lenvatinib therapy.
- To gain insights into the underlying mechanisms of lenvatinib-induced appetite loss.
Main Methods:
- Analysis of serum FGF21 levels at baseline, 1, 2, and 4 weeks post-lenvatinib initiation, and prior to appetite loss onset.
- Inclusion of 63 unresectable HCC patients treated with lenvatinib between 2018 and 2021.
- Comparison of FGF21 level changes between patients with and without grade ≥ 2 appetite loss.
Main Results:
- Serum FGF21 change rate significantly increased at 4 weeks post-lenvatinib initiation in patients who developed grade ≥ 2 appetite loss.
- Significant increases in serum FGF21 levels were observed prior to the onset of grade ≥ 2 appetite loss.
- No significant differences in baseline FGF21 levels were found between groups.
Conclusions:
- Changes in serum FGF21 levels can predict patients at higher risk of significant appetite loss during lenvatinib treatment for HCC.
- Elevated FGF21 levels may play a role in the mechanisms of lenvatinib-induced appetite loss.
- Identifying patients at risk for appetite loss can inform clinical management and improve prognosis in HCC patients.
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