Journal of Hepatocellular Carcinoma (Oct 2022)
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
Abstract
Ahmed O Kaseb,1 Yinghui Guan,2,* Betul Gok Yavuz,1,* Alexander R Abbas,2 Shan Lu,2 Elshad Hasanov,3 Han Chong Toh,4 Wendy Verret,5 Yulei Wang2 1Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, CA, USA; 3Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore; 5Product Development, Genentech Inc, South San Francisco, CA, USA*These authors contributed equally to this workCorrespondence: Yulei Wang, Department of Oncology Biomarker Development, Genentech Inc, 1 DNA Way, South San Francisco, CA, 94080, USA, Tel +1 650 255 9698, Email [email protected] Ahmed O Kaseb, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX, 77030, USA, Tel +1 713 792 2828, Email [email protected]: 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 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: IGF-CTP score, prognostic biomarker, immunotherapy, HCC
