Atezolizumab + bevacizumab versus lenvatinib as first-line systemic therapy for treatment of hepatocellular carcinoma in a real-world population: Outcomes from the HCC CHORD database.

4111 Background: Lenvatinib (LEN) and the combination of atezolizumab with bevacizumab (AB) are widely considered first-line systemic therapies for the treatment of advanced hepatocellular carcinoma (HCC), but have never been compared directly in a randomized clinical trial. Cross-trial comparisons between IMbrave150 and LEAP-002 appear to show similar survival outcomes for AB compared to LEN, respectively, while survival with LEN was shorter in the REFLECT trial. Methods: Patients treated with AB or LEN first-line for HCC from August 2018 to August 2022 in the Canadian provinces of British Columbia, Alberta, Manitoba, Nova Scotia and two centers in Ontario were included in this study. Demographic and clinical outcomes data were gathered. Statistical analysis identified the median OS, PFS, and physician-assess response rate (RR) associated with each treatment. Results: We identified 453 patients treated with first-line AB (n = 159) or LEN (n = 294). 85% were male, 14% had HBV, 32% HCV, 70% cirrhosis, 27% BCLC B disease, 69% BCLC C,37% distant metastasis, 88% Child-Pugh A, 87% ECOG 0-1 performance status and 55% had previous locoregional treatment. The two cohorts were balanced with respect to most demographic factors, but patients in the LEN cohort had higher incidence of ECOG Performance Status ≥ 2 (11% vs 5%; p = 0.047), lower incidence of HBV (12% vs 19%; p=0.047) and higher incidence of HCV (36% vs 25%; p=0.03). Median follow-up time of the AB cohort was 9.9 months (mos) compared to 11.8 mos for LEN. Median overall survival (mOS) of this HCC population was 15.4 mos. mOS was 19.7 mos (95% CI: 14.5-NR) in the AB cohort and 14.4 mos (95% CI: 12.2-17.1) in the LEN cohort (HR 0.72; 95% CI: 0.54-0.95; p=0.021). Median progression-free survival (mPFS) was 6.9 mos in the overall population, 8.3 mos for AB and 6.3 mos for LEN (HR 0.85; 95% CI: 0.68-1.06; p=0.20). RR was 29% overall, 31% for AB and 28% for LEN (p=0.50). LEN was the most common second-line treatment after AB (86%), while after LEN 46% of patients received regorafenib and only 21% received second-line AB. Conclusions: This study provided real-world efficacy outcomes for AB directly compared to LEN in the first-line treatment of HCC in a Western country. AB was correlated with superior OS compared to LEN, but PFS and RR appear to be similar.

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