Changes in Serum Growth Factors during Lenvatinib Predict the Post Progressive Survival in Patients with Unresectable Hepatocellular Carcinoma

Abstract

Serum growth factor changes and their effect on prognosis during lenvatinib for unresectable hepatocellular carcinoma (HCC) remain underexplored. The sequential changes in serum growth factors during lenvatinib for unresectable HCC were evaluated in 58 patients using complete clinical data, and preserved serum was used to investigate changes in FGF-19, ANG-2, HGF, VEGF, and EGF. Patients with a complete response (CR), partial response (PR), and stable disease (SD) were evaluated for growth factor changes between the best response and progressive disease (PD) points, classified based on these changes, and evaluated by post progression survival (PPS). A total of 8, 24, 18, and 8 patients showed CR, PR, SD, and PD, respectively. Multivariate analysis revealed that age, relative dose intensity, and baseline ANG-2 were significantly associated with treatment response. Growth factor changes between the best response and PD points revealed that patients could be classified into four groups based on the EGF, ANG-2, and HGF changes. Although patient characteristics at baseline and PD, their response to lenvatinib, and PFS were similar among those groups, patients with an increase in all growth factors had significantly shorter PPS (median PPS was 553, 323, and 316 versus 173 days in groups 1–4 p = 0.032). We revealed that the evaluation of the changes in growth factors during lenvatinib could predict PPS.

Systemic therapies in hepatocellular carcinoma: Existing and emerging biomarkers for treatment response

“…Similarly, recently, Yang et al. reported that higher baseline Ang-2 levels were significantly associated with a nonobjective response in HCC patients treated with lenvatinib ( 73 ).…”

“…Miyahara et al (68) described that Ang-2 had a similar predictive function as VEGFA and that Ang-2 levels were significantly elevated in patients with PD prior to sorafenib treatment. Similarly, recently, Yang et al reported that higher baseline Ang-2 levels were significantly associated with a nonobjective response in HCC patients treated with lenvatinib (73). Mechanism and pathways involved in the angiogenesis and proliferation of hepatocellular carcinoma and potential predictive biomarkers.…”

Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with Unresectable Hepatocellular Carcinoma

“…Recently, because of successful clinical trials of novel anticancer drugs for unresectable HCC, various systemic therapies, including multikinase inhibitors of sorafenib [ 3 ], lenvatinib [ 4 ], regorafenib [ 5 ], and cabozantinib [ 6 ], a monoclonal antibody targeting vascular endothelial growth factor receptor (VEGFR) 2, ramucirumab [ 7 ], and a combination therapy involving the anti-VEGF-A antibody bevacizumab and the programmed death ligand 1 (PD-L1) inhibitor atezolizumab [ 8 ] have been approved. Real-world data have confirmed the efficacy and safety of those therapies [ 9 , 10 , 11 , 12 , 13 , 14 ]. Of these, atezolizumab and bevacizumab have been recommended as the first-line therapies in various guidelines because they have shown superior overall survival (OS) as compared with the previous standard therapy of sorafenib [ 8 ].…”

“…We and other groups have reported that levels of fibroblast growth factors (FGFs), including FGF19 and FGF23, significantly increased after lenvatinib treatment for unresectable HCC [ 12 , 19 ]. Fibroblast growth factor 21 (FGF21) is a member of the FGF19 subfamily, which also includes FGF19 and FGF23.…”

Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150

“…Recent advances in systemic therapy have dramatically changed the treatment landscape for unresectable hepatocellular carcinoma (HCC), with prolonged overall survival (OS) [ 1 , 2 , 3 , 4 ]. Various systemic therapies have been developed for unresectable HCC, including the multikinase inhibitors sorafenib [ 1 ], regorafenib [ 5 ], cabozantinib [ 6 ], and lenvatinib [ 2 ], an antibody against VEGFR2, ramucirumab [ 7 ], and the combination of the programmed death ligand 1 (PD-L1) inhibitor atezolizumab and the VEGF inhibitor bevacizumab.…”