Supplementary Material for: Disease complexity and nodule-specific responses to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma

Background: Advanced hepatocellular carcinoma (HCC) presents a range of presentations and responses to immunotherapy. We sought to determine the effects of Atez/Bev in patients with advanced HCC and various prognostic factors.
Methods: We analyzed 183 patients with advanced HCC who received Atez/Bev and targeted the response patterns of 517 intrahepatic tumors and 88 extrahepatic tumors, organized by poor prognostic indicators: extrahepatic metastasis (EHM), microvascular invasion (MVI) and large intrahepatic tumors (≥5 cm).
Results: The median progression-free survival (PFS) and overall survival (OS) were recorded at 8.0 months and 22.6 months, respectively, with an objective response rate of 19.7%. Response patterns differed significantly for large intrahepatic tumors (≥5 cm): these tumors progressed more slowly than smaller tumors, accompanied by a similar incidence of new lesions and target lesion progression. The correlation between PFS and OS varied notably between patients with large tumors and those without, with correlation coefficients of 0.662 (95% CI 0.559–0.764) and 0.475 (95% CI 0.326–0.624), respectively. Intrahepatic lesions displayed homogenous responses (correlation coefficient = 0.682), while the correlation between intrahepatic and extrahepatic responses was weaker (correlation coefficient = 0.474). Tumors with MVI varied their response patterns according to their associated vascular invasion, although MVI did not influence survival. EHM affected PFS and OS, while tumor size only influenced OS.
Conclusions: Large intrahepatic tumors treated with Atez/Bev demonstrate prolonged stability, incomplete responses, and worse survival. The differing correlations between PFS and OS based on tumor size have significant implications for the design of clinical trials. This may indicate a potential advantage in incorporating locoregional interventions for treating large tumors in HCC strategies.