Real-World Data Show Similar Outcomes for First-Line uHCC Immunotherapy Regimens

Key Clinical Summary

• Real-world data from 6 US cancer centers showed no significant difference in overall survival or treatment duration between atezolizumab plus bevacizumab and durvalumab plus tremelimumab as first-line therapy for unresectable hepatocellular carcinoma (uHCC).
• Median overall survival was approximately 14 to 15 months with both regimens, with disease progression the most common reason for discontinuation.
• Child-Pugh class at treatment initiation was a strong prognostic factor, with markedly worse outcomes in patients with more advanced liver dysfunction.

Unresectable hepatocellular carcinoma remains a leading cause of cancer-related mortality in the US, with limited comparative evidence to guide first-line systemic therapy selection. A multicenter real-world analysis evaluated outcomes with atezolizumab plus bevacizumab and durvalumab plus tremelimumab, 2 US Food and Drug Administration (FDA)-approved regimens, using data from 6 tertiary US cancer centers.

Study Findings

Investigators retrospectively analyzed electronic health records from 452 patients with uHCC who initiated first-line atezolizumab/bevacizumab or durvalumab/tremelimumab between March 2017 and February 2024. The study included patients treated at Mayo Clinic and its health system sites, Cleveland Clinic–affiliated centers, the University of Alabama, Cedars-Sinai Medical Center in Los Angeles, and the University of Michigan.

The median patient age was 68 years, 77% were male, and 81% were White. Viral hepatitis (38.9%) and metabolic dysfunction-associated steatohepatitis (19.5%) were the most common underlying etiologies. Overall survival (OS) and time to treatment discontinuation (TTD) were assessed using Kaplan-Meier and Cox regression models with adjustment for baseline characteristics.

Clinical outcomes did not significantly differ between regimens. Median OS was 14.0 months with atezolizumab/bevacizumab and 14.6 months with durvalumab/tremelimumab (P = .66). Median TTD was 4.9 months and 3.9 months, respectively (P = .42). Disease progression was the leading cause of treatment discontinuation in both groups, reported in 56% of patients receiving atezolizumab/bevacizumab and 42% receiving durvalumab/tremelimumab.

In contrast, outcomes varied substantially by liver function. Median OS declined from 19.0 months in Child-Pugh class A to 6.1 months in B7, 5.1 months in B8/9, and 2.0 months in class C (P < .001). A similar pattern was observed for TTD, ranging from 6.1 months in class A to 1.3 months in class C.

Clinical Implications

For oncology leaders and pathway decision-makers, these findings suggest that atezolizumab/bevacizumab and durvalumab/tremelimumab offer comparable real-world effectiveness as first-line options for uHCC in US practice. In the absence of statistically significant differences in survival or treatment durability, regimen selection may reasonably hinge on patient-specific factors, comorbidities, contraindications, and payer considerations.

The strong prognostic impact of Child-Pugh class reinforces the central role of baseline liver function in therapeutic decision-making and outcomes assessment. Patients with Child-Pugh B or C disease experienced substantially shorter survival and treatment duration regardless of regimen, highlighting an unmet need for optimized strategies in this population. For payers and pathway developers, the data support flexibility between these regimens while emphasizing careful patient stratification by hepatic reserve.

According to the study investigators, this large multicenter real-world analysis demonstrated “no statistically significant differences in overall survival, objective response, and time to treatment discontinuation” between the 2 first-line immunotherapy-based regimens for uHCC. The authors emphasized that Child-Pugh score emerged as a key prognostic variable across both treatments, underscoring liver function as a dominant driver of outcomes in routine US oncology practice.

Conclusion

In a large US real-world cohort, atezolizumab/bevacizumab and durvalumab/tremelimumab produced similar clinical outcomes as first-line therapy for unresectable hepatocellular carcinoma. Child-Pugh class strongly influenced prognosis, informing clinical pathways while future studies explore toxicity and quality-of-life differences.

Reference

Kournoutas I, Marell P, Gile J, et al. First-line atezolizumab/bevacizumab or durvalumab/tremelimumab in advanced hepatocellular carcinoma: a real world, multicenter retrospective study. Oncologist. 2025;30(11):oyaf286. doi: 10.1093/oncolo/oyaf286