Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

Abstract

Background: Sorafenib and lenvatinib are first-line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear. Methods: We identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2-3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long-SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated. Results: Overall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib. Conclusion: This study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC.

Pharmacodynamic Biomarkers Predictive of Survival Benefit with Lenvatinib in Unresectable Hepatocellular Carcinoma: From the Phase III REFLECT Study

“…Author Manuscript Published OnlineFirst on June 9, 2021; DOI: 10.1158/1078-0432.CCR-20-4219 pharmacodynamic biomarker for FGFR inhibitors in patients with cancer (29). A significant association was reported between baseline serum FGF19 levels and treatment response to lenvatinib in a biomarker analysis of uHCC patients treated with lenvatinib or sorafenib (30).…”

Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma

“…In conclusion, our study demonstrated that Ang2 is a potential novel biomarker for both diagnosis and prognosis in HCC. It has been demonstrated that baseline Ang2 level is related to the treatment effect of sorafenib and lenvatinib 38 , 39 . Considering the central role of angiogenesis-inhibiting therapy in recent drug therapies for HCC 40 , 41 , it may be of marked significance as a biomarker for predicting therapeutic efficacy and making a prognosis.…”

Baseline serum angiopoietin-2 and VEGF levels predict the deterioration of the liver functional reserve during lenvatinib treatment for hepatocellular carcinoma

“…Serum VEGF, ANG2, FGF19, and FGF21 levels were evaluated using commercial enzyme-linked immunosorbent assays (VEGF, ANG2, and FGF19: R&D Systems, Minneapolis, MN, USA; FGF21: Merck Millipore, Darmstadt, Germany) according to the manufacturers’ protocols [ 14 ].…”

“…Lenvatinib, which targets VEGFR1-3, fibroblast growth factor receptors 1-4, plateletderived growth factor receptor-α, c-Kit, and rearranged during transfection proto-oncogene [11,12], demonstrated non-inferiority to sorafenib in terms of OS in unresectable HCC [8]. The efficacy and safety of lenvatinib in patients with unresectable HCC have been demonstrated in a real-world setting [13][14][15][16][17]. However, some patients experienced deterioration of the liver functional reserve during lenvatinib treatment for HCC.…”