OBJECTIVES : Sorafenib (SOR) and lenvatinib (LEN) are reimbursed in Portugal for patients with unresectable hepatocellular carcinoma (uHCC). The combination of atezolizumab and bevacizumab (A+B) presents a new therapeutic option for these patients. This study aimed to indirectly compare the clinical efficacy and safety of A+B to both SOR and LEN for the first-line treatment of uHCC.

METHODS : A systematic literature review (SLR) was performed to identify all relevant studies that could contribute to a network of evidence between the interventions of interest. All randomised controlled trials reporting results for the first-line treatment of patients with uHCC were included. Outcomes of interest included overall survival (OS), progression free survival (PFS), response rates (RR), duration of response, and quality of life (QoL) assessment, as well as any safety-related outcomes. Indirect treatment comparisons (ITC) to estimate the relative treatment effects for each outcome were generated using Bucher’s method.

RESULTS : A total of 80 references were included in the qualitative analysis of the SLR. However, only two studies actively contributed to estimate the treatment effects between the three interventions of interest: IMbrave150 (A+B versus SOR) and REFLECT (LEN versus SOR). Relative treatment effects between A+B and SOR are obtained directly from the IMbrave150 study, where A+B has shown a superiority on all efficacy outcomes and comparable results on all safety outcomes. The ITC results estimate that A+B significantly reduces the risk of death by 37% (HR=0.63; 95%CI: 0.44 – 0.89) and the risk of a clinically meaningful deterioration of QoL scores by 38% (HR=0.62; 95%CI: 0.44 – 0.88), when compared to LEN. The results also show comparability between interventions regarding the PFS, RR, and all safety outcomes.

CONCLUSIONS : The combination of A+B has proven to have superior efficacy and a similar safety profile to both SOR and LEN for the first-line systemic treatment of patients with uHCC.