Second-line Treatment Strategy in Unresectable Hepatocellular Carcinoma After First-line Atezolizumab Plus Bevacizumab

Abstract

Background/aim: Atezolizumab plus beva-cizumab (AteBev) are an integral part of first-line therapy for unresectable hepatocellular carcinoma (uHCC), whereas no second-line regimen has been developed for these patients. This study evaluated the efficacy of second-line therapy for uHCC following AteBev treatment.

Patients and methods: Sixty uHCC patients who were administered AteBev therapy were included in the study. Dynamic computed tomography was conducted after 6, 9, and 12 weeks, and blood tests were performed at baseline and after three weeks.

Results: After six weeks of AteBev therapy, 19 patients experienced partial response (PR), 12 had stable disease (SD), and 29 exhibited progressive disease (PD), with an overall response rate (ORR) of 31.7%. Of the 21 patients treated with lenvatinib as second-line treatment, one dropped out, nine experienced a compete response (CR) or PR, and 11 had SD or PD, resulting in an ORR of 45.0%. Serum levels of fibroblast growth factors (FGF)-19 increased substantially following lenvatinib therapy in the CR+PR group, although the levels decreased significantly in the SD+PD group. Soluble FGF-R4 levels did not differ significantly between the CR+PR group and the SD+PD group when assessed before and after lenvatinib treatment.

Conclusion: Lenvatinib is useful as second-line treatment after Ate/Bev for uHCC patients who do not response to Ate/Bev treatment. Changes in serum FGF-19 levels after three weeks of AteBev therapy may serve as a biomarker for selecting lenvatinib as second-line therapy.

Keywords: Atezolizumab; bevacizumab; cabozantinib; hepatocellular carcinoma; lenvatinib; second-line.