Safety, Efficacy, and Outcomes of 90-Yttrium Radioembolization in Combination with Immune Checkpoint Inhibitors as a Definitive First-Line Treatment Approach in Non-Surgical Hepatocellular Carcinoma

Monday, March 31, 2025

4:03 PM – 4:12 PM CT

Location: Music City Center, 208 AB

Presenting Author(s)

TS

Tyler Sandow, MD

Interventional Radiologist
Ochsner Health, United States

Author/Co-author(s)

AG

Alexandre Grahovac, BS

PGY4
Ochsner Clinical School, United States
JM

Jonathan Mizrahi, MD

Hematology-Oncology
Ochsner Clinic Foundation, United States
LD

Lingling Du, MD

Hematology/Oncology
Ochsner Clinic Foundation, United States
RV

Ricardo Vallejo-Calzada, MD

Hematology/Oncology
Ochsner Clinic Foundation, United States
Juan Gimenez, MD

Interventional Radiologist
Oschner Health, United States
AC

Ari Cohen, MD

Medical Director of Multi-Organ Transplant Institute
Multi-Organ Transplant Institute, Ochsner Health, New Orleans, LA, 70121, United States
KN

Kelley Nunez, PhD

United States
PT

Paul Thevenot, PhD

Associate Professor
Ochsner Clinic Foundation, United States

Purpose: Immune checkpoint inhibitors (ICI) have emerged as first line therapy for advance-stage HCC. However, response rates remain modest (< 20%). Combination treatments offer potential to improve initial response rates and extend duration of response. While early studies of ⁹⁰Y-ICI showed fewer adverse events (AE) and improved objective responses (OR) (30-40%), there were no improvements in time to progression (TTP) and overall survival (OS). This study evaluates safety, efficacy, and outcomes of first line ⁹⁰Y-ICI and the role of ICI regimen and treatment sequencing.

Materials and Methods: A retrospective, multi-center study was conducted in BCLC A-C stage HCC patients (ECOG 0-1) receiving first line ⁹⁰Y-ICI with atezolizumab/bevacizumab (A+B) or tremelimumab/durvalumab (STRIDE). Treatment response was recorded at ⁹⁰Y follow-up. TTP, progression-free survival (PFS), and OS were primary endpoints, with AE and safety as secondary outcomes.

Results: The study included 40 patients receiving ⁹⁰Y-ICI from 2021–2024 (12 months median follow-up). The cohort was predominantly Child-Pugh A (96%) with HCV-related cirrhosis (76%), BCLC-C stage (51%), and a median target HCC size of 7.7 cm (IQR, 6-11 cm). Grade 3-4 AEs occurred in 15 patients (37%), leading to steroid use (12, 29%), treatment delays (13, 31%), or discontinuation (4, 10%). The first cycle target OR rate was 82% (32/39), with a 51% (20/39) complete response (CR) rate with overall OR of 59% (23/39), with a 41% (16/39) CR rate. No differences were found in adverse events, delays, or discontinuations based on sequencing or regimen.

Sequencing and ICI regimen had no effects on target or overall OR and no downstream effect on TTP or PFS, although the data trended toward higher response rates with the STRIDE regimen. Log-rank analysis revealed target CR was associated with improved TTP (P = 0.004) and PFS (P = 0.009), but not OS (P = 0.237). Achieving an overall CR was associated with further improvements in TTP (P < 0.001) and PFS (P < 0.001). The cohort 2-year OS was 55% with median OS not yet reached.

Conclusion:

First line ⁹⁰Y-ICI therapy in BCLC A-C stage HCC is an effective treatment strategy with AEs in the expected range of systemic therapy and low rates of treatment discontinuation. Sequencing and ICI regimen did not significantly impact AEs or treatment outcomes. However, patients achieving CR showed significantly improved TTP and PFS. Although follow-up is limited, these findings suggest achieving CR is key to optimal long-term outcomes. We anticipate long-term follow-up will demonstrate an OS benefit linked to first line CR rate.