Faiza Ahmed1, Prathima Guntipalli2, Zeynep Yukselen3, Maria-Kassandra Coronel1, Madiha Zaidi1, Jennifer Onwumeh-Okwundu4, Vamsi Garimella5, Sravya Gudapati6, Marc-Darlene Mezidor7, Kim Andrews8, Mohamad Mouchli9, Endrit Shahini10, Karthik Mohan11

1Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, United States of America, 2School of Business and Healthcare Administration, Texas Woman’s University, Denton, Texas, United States of America, 3School of Public Health and Health Sciences, University of Massachusetts, Amherst, United States of America, 4Department of global health, Faculty of medical sciences Stellenbosch University, Cape town ,South Africa, 5Department of Internal Medicine, University of Miami SOM, Holy Cross Health, Lauderdale, Florida, United States of America, 6College of Medicine, Washington University of Health and Science, San Padro, Belize, 7Department of Radiology, Amita Health Saint Francis Hospital, Evanston, Illinois , United States of America, 8Department of Mathematics and Natural Sciences, Prince Mohammad Bin Fahad University, Al Khobar, Saudi Arabia, 9Department of Gastroenterology, Cleveland Clinic, Cleveland, Ohio, United States of America, 10Gastroenterology Unit, Institute for Cancer Research and Treatment, Candiolo, Turin, Italy, 11Department of Gastroenterology, Larkin Community Hospital, South Miami, Florida, United States of America

Background/Aims: Sorafenib has been the historical first-line treatment of choice for unresectable or metastatic hepatocellular carcinoma (HCC) since the year 2007. However, on May 29, 2020, FDA approved atezolizumab plus bevacizumab (AB) combination for HCC and gave it priority over sorafenib. Here, we performed a systematic review evaluating the efficacy and safety of combination immunogenic chemotherapy as first-line therapy as opposed to sorafenib (S) and atezolizumab (A) monotherapies.

Methods: A literature search of only randomized clinical trials was conducted in nine databases until February 2021. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2).

Results: We obtained 520 articles and included two eligible randomized clinical trials (RCTs), Finn et al. (2020) and Lee et al. (2020). Both studies presented less mortality rate for AB compared to A versus S groups [96(28.6%),p=0.0033;16(27%),0(0%); vs. 18(31%); vs. 65(39.4%),p=0.0033]. Overall survival (OS) rate at 6 and 12 months was higher in AB versus S group [84.8% (95%Cl,80.9-88.7); 67.2%(95%Cl,61.3-73.1); vs.72.2%(95%Cl,80.9-88.7); 54.6%(95%Cl,45.2-64)]. Median progression-free survival was superior for AB in both studies compared to A and S groups [6.8months(95%Cl,5.7-8.3) ;7.3months(95%Cl,5.4-9.9); 5.6months(95%Cl,3.6-7.4) vs. 3.4months(95%Cl,1.9-5.2) vs. 4.3months(95%Cl,4.0-5.6)]. Disease control rate was significantly lower in A group and highest in AB group [(29(49%) vs. 240(73.6%),74(71%),40(67%)]. Most common grade 3-4 adverse events were hypertension and proteinuria reported in all groups. For more information, refer to Table 1.

Conclusion: Atezolizumab-bevacizumab is a better first-line treatment for unresectable HCC than sorafenib or atezolizumab monotherapy since it has longer progression-free survival, delayed time to deterioration, and a better overall tumor response.

Keywords: hepatocellular carcinoma, atezolizumab-bevacizumab, sorafenib, atezolizumab, randomized clinical trials