Supplementary Material for: Lenvatinib as second-line treatment after atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma –clinical results show importance of hepatic reserve function

Background/Aim: Lack of an established methodology for post-progression systemic treatment following atezolizumab plus bevacizumab (Atez/Bev) administration is an important clinical issue. The present study aimed to elucidate the potential of lenvatinib as a second-line treatment option after Atez/Bev failure. Materials/Methods: From 2020 to 2022, 101 patients who received lenvatinib as second-line treatment were enrolled (median 72 years, males 77, Child-Pugh A 82, BCLC-A:B:C:D=1:35:61:4), while 29 treated with another molecular targeting agent (MTA) during the period as second-line treatment were enrolled as controls. The therapeutic efficacy of lenvatinib given as second-line treatment was retrospectively evaluated. Results: Median progression-free survival/median overall survival for all patients was 4.4/15.7 months and for those with Child-Pugh A was 4.7 months/not-reached. When prognosis was compared with patients who received another MTA, there was no significant difference for PFS (3.5 months, P=0.557) or OS (13.6 months, P=0.992), and also no significant differences regarding clinical background factors. mRECIST findings showed that objective response and disease control rates in patients treated with lenvatinib were 23.9% and 70.4%, respectively (CR:PR:SD:PD=3:14:33:21), while those shown by RECIST, ver. 1.1, were 15.4% and 66.2%, respectively (CR:PR:SD:PD=1:10:36:24). Adverse events (any grade ≥10%) were appetite loss (26.7%) (grade 1:2:3=2:15:10), general fatigue (21.8%) (grade 1:2:3=3:13:6), protein in urine (16.8%) (grade 1:2:3=0:4:13), and hypertension (13.9%) (grade 1:2:3=1:8:5). Conclusion: Although lenvatinib treatment might not provide a pseudo-combination immunotherapy effect following Atez/Bev failure, lenvatinib when used as second-line treatment after Atez/Bev failure might be expected to be comparable as compared to its use as first-line treatment.