Serum IGF-1 Scores and Clinical Outcomes in the Phase III IMbrave150 Study of Atezolizumab Plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma

Ahmed O Kaseb; Yinghui Guan; Betul Gok Yavuz; Alexander R Abbas; Shan Lu; Elshad Hasanov; Han Chong Toh; Wendy Verret; Yulei Wang

doi:10.2147/JHC.S369951

Serum IGF-1 Scores and Clinical Outcomes in the Phase III IMbrave150 Study of Atezolizumab Plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2022 Oct 11:9:1065-1079. doi: 10.2147/JHC.S369951. eCollection 2022.

Authors

Affiliations

¹ Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, CA, USA.
³ Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
⁵ Product Development, Genentech Inc, South San Francisco, CA, USA.

^# Contributed equally.

Abstract

Purpose: Child-Turcotte-Pugh class A (CTP-A) in unresectable hepatocellular carcinoma (HCC) is the standard criterion for active therapy and clinical trial enrollment. We hypothesized that insulin-like growth factor-1 (IGF-1) derived scores may provide improved survival prediction over CTP classification. This study aimed to evaluate the potential prognostic and predictive effects of IGF-1 derived scores in the phase III IMbrave150 study.

Patients and methods: Baseline and on-treatment serum IGF-1 levels from 371 patients were subjected to central analysis. Patients' IGF-1 score (1/2/3) and IGF-CTP score (A/B/C) were determined based on pre-specified cutoffs. Outcomes were analyzed by baseline and by on-treatment changes of the IGF-1 and IGF-CTP scores within and between the two treatment arms. The interaction between these scores and outcomes was assessed using univariate and multivariate analyses.

Results: Baseline IGF-CTP score (A vs B/C) showed prognostic significance for OS in both the atezolizumab-bevacizumab (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.20-0.56; P<0.001) and sorafenib (HR, 0.32; 95% CI, 0.16-0.65; P=0.002) arms. Baseline IGF-1 score (1 vs 2/3) also showed prognostic significance for OS in both the atezolizumab-bevacizumab (HR, 0.33; 95% CI, 0.20-0.55; P<0.001) and sorafenib (HR, 0.48; 95% CI, 0.26-0.89; P=0.02) arms. HRs for PFS were consistent with those for OS. No significant predictive effects were observed for either score between the two arms. Kinetic analysis revealed that patients with increased IGF-1 score (1-> 2/3) at 3 weeks post treatment had shorter OS than patients with stable IGF-1 score of 1 in both the atezolizumab-bevacizumab (HR, 3.70; 95% CI, 1.56-8.77; P=0.003) and sorafenib (HR, 5.83; 95% CI, 1.88-18.12; P=0.0023) arms.

Conclusion: Baseline and kinetic change of IGF-CTP and IGF-1 scores are independent prognostic factors for patients with unresectable HCC treated with atezolizumab-bevacizumab or sorafenib. These novel scores may provide improved patient stratification in future HCC clinical trials. IMbrave150 ClincialTrials.gov number, NCT03434379.

Keywords: HCC; IGF-CTP score; immunotherapy; prognostic biomarker.

Associated data

ClinicalTrials.gov/NCT03434379

Grants and funding

This study was funded by F. Hoffmann-La Roche/Genentech. Editorial support was provided by Jennifer Sollenberger of Health Interactions, funded by the sponsor.