Background: Atezolizumab plus bevacizumab (ATEZO/BEV) and lenvatinib (LEN) have shown efficacy as first-line systemic treatments for unresectable hepatocellular carcinoma (HCC) in previous studies. This study aimed to compare the efficacy, safety, and outcomes of two treatments in patients with unresectable HCC. In addition, we assess the potential predictors of response after LEN or ATEZO/BEV therapy.

Methods: Data were retrospectively collected from 130 patients with unresectable HCC who received LEN (n=52) and ATEZO/BEV (n=78) as first-line therapies between 2020 and 2023 at Chulalongkorn University Hospital, Thailand. The objective response was defined based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Results: Overall, patients had a mean age of 60.7 ±12.5 years, 107 patients (82.3%) were male, and 66.2% had hepatitis B or C viral infection. Ninety-seven patients (74.4%) were classified as HCC Barcelona Clinic Liver Cancer (BCLC) stage C and 82 patients (63.1%) had Child-Pugh (CTP) A. Treatment with ATEZO/BEV had no significant difference in median progression-free survival (PFS) (7.1 vs. 5.4 months, HR=1.38 95%CI 0.62-3.05, p=0.43) but significantly superior median overall survival (OS) (10.6 vs. 7.0 months, HR=2.02 95%CI 1.07-3.84, p=0.03) compared to LEN. Objective response rate (ORRs) was not significantly different between ATEZO/BEV and LEN (23.1% vs. 19.2%, p=0.60). Multivariate analyses revealed that extrahepatic metastasis, BCLC stage C, total bilirubin, serum sodium, and serum alpha-fetoprotein were associated with the treatment response of ATEZO/BEV, while non-viral etiology, BCLC stage C, CTP A, and age were associated with the treatment response of LEN. Adverse events, particularly diarrhea and fatigue, were significantly more common in the LEN group, whereas ATEZO/BEV exhibited higher rates of infection and gastrointestinal bleeding. Liver decompensation was found in 14.1% with ATE/BEV compared to 15.4% in the LEN group (p=0.84).

Conclusion: First-line treatment with ATEZO/BEV exhibited superior overall survival outcomes than LEN in patients with unresectable HCC. While ORRs and PFS did not significantly differ between ATEZO/BEV and LEN.

<b>Table 1. </b>Patient Characteristics at Baseline

Table 1. Patient Characteristics at Baseline

<b>Figure 1. A</b> Progression-free survival and <b>B </b>overall survival in unresectable hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab or lenvatinib

Figure 1. A Progression-free survival and B overall survival in unresectable hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab or lenvatinib

Sangdao Boonkaya

Appearances