First line atezolizumab + bevacizumab (atezo/bev) or durvalumab ± tremelimumab (durva±treme) in unresectable hepatocellular carcinoma (HCC): A real world, multi-institutional retrospective cohort study.
Authors: Kournoutas Ioannis , Marell Paulina S , Peersen Anina , Gupta Garima , Akce Mehmet , Yang Ju Dong , Chen Pin-Jung , Naleid Nikolas , Mahipal Amit , Sahai Vaibhav , Thompson Scott , Jin Zhaohui , Venkatesh Sudhakar , Borad Mitesh J. , Babiker Hani M. , Bekaii-Saab Tanios S. , McWilliams Robert R. , Halfdanarson Thorvardur Ragnar , Ou Fang-Shu , Tran Nguyen H. 
Published: January 2025

532

Background:
HCC accounts for 80% of primary liver cancers, and worldwide, is the third common cause of cancer-related death. Two FDA approved 1st line systemic treatment options include atezo/bev and durva ± treme. Herein we report outcomes of these regimens in the 1st line setting via a real-world, multi-institutional retrospective cohort study.
Methods:
We reviewed clinical outcomes of patients (pts) who initiated 1st line atezo/bev or durva ± treme for unresectable HCC between March 2017 and February 2024, across 5 institutions (Mayo Clinic, University of Alabama, Cedars-Sinai Medical Center, University Hospitals Seidman Cancer Center and University of Michigan). Time to treatment failure (TTF) and overall survival (OS) were analyzed using the Kaplan-Meier method. Best (objective) response was tabulated. Multivariable analyses were performed using Cox models and logistic regression for time-to-event and binary outcomes, respectively, while adjusting for age, sex, race, HCC etiology, Child-Pugh class, and ALBI grade.
Results:
A total of 433 HCC pts were included; atezo/bev (336), durva ± treme (97). Median age at the start of therapy was 68 years; 77% were male, 82% were Caucasian. Etiologies of HCC were viral hepatitis (38%), MASLD (20%), alcohol (10%), non-viral multifactorial (10%), or unknown (22%). Pts receiving durva ± treme were less likely to have cirrhosis (11% vs. 28%, p<0.01) but similar in terms of macrovascular invasion (63% vs. 58%, p=0.35) compared to pts receiving atezo/bev. Reasons for treatment discontinuation were similar between the two groups, with the most common being disease progression - atezo/bev (56%) and durva ± treme (47%). The differences in clinical outcomes were not statistically significantly and remained consistent after multivariable adjustment. (Table, atezo/bev as the reference group). Outcomes were significantly different between Child-Pugh classes (CP: A,B,C) respectively, OS: 19.0 m, 6.4 m, 1.9 m (p<0.001); TTF: 6.1 m, 2.7 m, 1.3 m (p<0.001).
Conclusions:
In this real-world retrospective cohort study of unresectable HCC, the differences in overall survival, objective response, and time to treatment failure were not statistically significant between atezo/bev and durva ± treme in the 1st line setting.

Outcome
Atezo/bev
Durva±treme
Univariate p-value
Multivariable adjusted hazard ratio (95% CI)
Multivariable adjusted odds ratio (95% CI)

Overall Survival, Median (month)
14.0
14.6
0.77
0.78 (0.54-1.14)
---

Time to Treatment Failure, Median (month)
4.9
4.1
0.71
0.95 (0.72-1.26)
---

Objective response, %
26.3%
21.1%
0.31
---
0.78 (0.43-1.39)