Atezolizumab plus bevacizumab is associated with improved survival outcomes in HCC patients with Child-Pugh B dysfunction compared to best supportive therapy

Atezolizumab plus bevacizumab (A+B) is the recommended first line for unresectable HCC (uHCC) in patients with well-preserved liver function. Emerging evidence supports the safety of this approach even in patients with Child-Pugh B (CPB) liver dysfunction. Whether CPB patients benefit from active anti-cancer treatment as opposed to best supportive therapy (BST) remains under debate. Here we report survival outcomes of CPB patients receiving A+B in routine practice compared to a cohort of patients receiving BST using inverse probability of treatment weighted (IPTW) analysis.

Data of 136 uHCC CPB patients receiving first-line systemic therapy with A+B from January 2020 to December 2022 were extracted from an international consortium and compared to a cohort of 159 CPB patients receiving BST, extracted from the ITA.LI.CA database. To reduce the differences in baseline characteristics, propensity score was calculated using the following variables: alpha-fetoprotein (AFP) (≥400vs 2). A+B exposure was evaluated in relationship with OS using IPTW multivariate Cox regression models. All the 95% confidence intervals (CIs) from multivariable Cox regression were corrected using a dataset-specific conditional interpretation with frailty model.

In the IPTW populations, patients receiving A+B reported a median OS of 7.73 months (95%CI: 5.9-12.5) compared to 4.04 months (95%CI: 3.0-5.0) of patients receiving BST, which was associated with a marginal, but significant reduction in the risk of death (HR: 0.61; 95%CI: 0.4-0.9, p=0.011). The IPTW fitted multivariate model showed A+B to be associated with a significant reduction in the risk of death (HR: 0.52; 95%CI 0.4-0.8). AFP ≥400 (HR: 1.84; 95%CI: 1.3-2.7); EHS (HR: 1.41; 95%CI: 1.0-1.9) and the presence of PVTT (HR: 1.89; 95%CI: 1.3-.2.7) were associated with significantly worse prognosis. In the A+B -exposed group, incidence of all-causes adverse events (AEs) of all grades was 66.1%, 11.8% the incidence of grade 3 AEs and 8% the incidence of AEs leading to permanent treatment discontinuation. No Grade 5 AE was reported. Overall, 18 (13.2%) patients in the A+B arm experienced bleeding events (grade 1: 9, grade 2: 3, grade 3: 6). Among them, 8 were related to esophageal varices (4 grade 3), no grade 5 bleeding events were reported.

Systemic treatment with A+B was associated with a small but significant OS improvement in CP-B patients compared to BST. IPTW OS estimates corrected for patient origin indicated extended survival times in patients with no EHS, AFP < 400ng/mL and no PVTT, identifying a patient sub-population where A+B may be delivered with higher clinical benefit. This retrospective study provides preliminary but convincing controlled evidence of improved survival from A+B exposure compared to BST in CPB patients.

The authors.

Has not received any funding.

A. D'Alessio: Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Roche. M. Pinter: Honoraria (self): AstraZeneca, Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche; Advisory / Consultancy: AstraZeneca, Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche; Speaker Bureau / Expert testimony: Bayer, BMS, Eisai, Lilly, MSD, and Roche; Research grant / Funding (institution): Roche; Travel / Accommodation / Expenses: Bayer, BMS, and Roche. A. Vogel: Honoraria (self): AstraZeneca, Amgen, BeiGene, Böhringer Mannheim, BMS, BTG, Daichi-Sankyo, EISAI, GSK, Imaging Equipment Ltd (AAA), Incyte, Ipsen, Jiangsu Hengrui Medicines MSD, PierreFabre, Roche, Servier, Sirtex, Tahio, Terumo; Advisory / Consultancy: AstraZeneca, Amgen, BeiGene, Böhringer Mannheim, BMS, BTG, Daichi-Sankyo, EISAI, Incyte, Ipsen, MSD, PierreFabre, Roche, Servier, Sirtex, Tahio, Terumo. P. Galle: Honoraria (self): Bayer, Boston Scientific, AstraZeneca, Adaptimmune, BMS, Eisai, MSD, Sirtex, Lilly, Roche, Guerbet, Ipsen.; Advisory / Consultancy: Bayer, Boston Scientific, AstraZeneca, Adaptimmune, BMS, Eisai, MSD, Sirtex, Lilly, Roche, Guerbet, Ipsen.; Speaker Bureau / Expert testimony: Bayer, Boston Scientific, AstraZeneca, Adaptimmune, Eisai, Sirtex, Roche, Ipsen.; Research grant / Funding (self): Bayer, Roche; Travel / Accommodation / Expenses: Roche, AstraZeneca, Sirtex, Ipsen. M. Kudo: Honoraria (self): Eli Lilly, Bayer, Eisai, Chugai, Takeda, AstraZeneca; Advisory / Consultancy: Chugai, Roche, AstraZeneca, Eisai; Research grant / Funding (institution): Taiho, Otsuka, EA Pharma, AbbVie, Eisai, Chugai, GE Healthcare. A. Singal: Advisory / Consultancy: Genentech, AstraZeneca, Eisai, Bayer, Exelixis. E. Giannini: Advisory / Consultancy: AstraZeneca, Roche; Speaker Bureau / Expert testimony: EISAI, MSD, Roche. All other authors have declared no conflicts of interest.