Patient (pt) characteristics, treatment patterns, and outcomes in unresectable hepatocellular carcinoma (uHCC) treated with first-line (1L) systemic therapy in the United States (US).
Authors: Tran Nguyen H. , Soefje Scott A. , Rangarajan Nivedita , Purushotham K , Nadig Mihika , Wagner Tyler E. , Valerio Stephen J. , Anderson Rye , Olson Jody C. 
Published: January 2025

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Background:
Guidelines recommend systemic therapy for uHCC ineligible for locoregional therapy. Until the approval of tremelimumab + durvalumab for uHCC, in Oct 2022, 1L systemic therapies in the US included multikinase inhibitors and atezolizumab (A) + bevacizumab (B). It is crucial to understand factors driving real-world treatment decisions and outcomes in uHCC. Characteristics, treatment patterns, and outcomes were assessed in US pts with uHCC treated with 1L systemic therapy.
Methods:
Data were collected from electronic medical records from US Mayo Clinic sites. Pts with uHCC who initiated an NCCN-recommended 1L systemic therapy between Jun 2020–Oct 2022 (A + B was the only approved 1L immunotherapy (IO)-based regimen) with ≥2 follow-up visits, were included. Index was the date of first 1L systemic therapy. Pts were assessed by risk of post-index gastrointestinal (GI) bleeding (pts with Child-Pugh class B or C, pre-index GI bleeding, uncontrolled hypertension [HTN] [≥2 anti-HTN drugs or ≥2 vital entries of SBP >140 mmHg or DBP >90 mmHg]), or significant varices and band ligation). Treatment patterns, overall survival (OS), and post-index GI bleeding were assessed.
Results:
A total of 186 pts met the inclusion criteria. Most common etiologies of liver disease were metabolic dysfunction-associated steatohepatitis (42.7%) and hepatitis C virus (40.2%). Pre-index GI bleeding was reported in 29.0% of pts, of which 46.3% occurred within 6 months (mo) pre-index; 62.4% of pts had EGD, of which 72.4% had varices. There were 128 (68.8%) pts with GI bleeding risk and 58 (31.2%) pts without GI bleeding risk. The most common 1L systemic therapies for pts with GI bleeding risk were A + B (72.7%) and A only (9.4%), while for pts without GI bleeding risk, A + B (29.3%), nivolumab + ipilimumab (13.8%), and B + chemotherapy (13.8%) were the most common. Median OS and OS rates at 12, 18, and 24 mo were lower, and post-index GI bleeding rate was higher in pts with vs without GI bleeding risk (Table). For pts treated with A + B, median OS and OS rates at 12, 18, and 24 mo were lower in pts with vs without GI bleeding risk (Table).
Conclusions:
In this network, prior to the approval of other 1L IO-based regimens for uHCC, many pts received A + B, despite risk of post-index GI bleeding. Median OS with A + B was shorter in pts with vs without GI bleeding risk. Data highlight the complexity of uHCC and the unmet need for guidance on characteristics-driven treatment decisions.

Full cohort

A + B cohort

All ptsN=186

GI bleeding risk
N=128

No GI bleeding risk N=58

All pts
N=110

GI bleeding risk
N=93

No GI bleeding risk
N=17

Median follow-up, mo
20.6
20.9
20.4
21.3
21.6
20.3

Median OS, mo
14.4
11.4
40.3
13.9
12.8
Not reached

OS rates, %

12 mo
55.2
48.9
68.9
55.2
52.3
70.6

18 mo
45.3
38.1
61.1
44.1
41.6
57.8

24 mo
39.4
31.8
56.8
37.1
34.6
51.3

Post-index GI bleed, %
17.2
23.4
3.4
17.3
19.4
5.9