Background: Hepatocellular carcinoma is the fifth most common cancer worldwide and the third leading cause of cancer-associated deaths. In 2020, the positive results of the IMbrave 150 trial and FDA (Food and Drug Administration) approval subsequently revolutionized the management of non-resectable hepatocellular carcinoma as the first-line treatment. However, their role as second-line therapy in people refractory to systemic therapy needs to be better studied. We perform a comprehensive literature review evaluating outcomes of atezolizumab plus bevacizumab in patients refractory to first-line systemic therapy. Methods: We performed a comprehensive literature search of PubMed, Embase, and Cochrane, evaluating the outcomes of atezolizumab plus bevacizumab in patients refractory to first-line systemic therapy. Results:Conclusions: Atezolizumab plus Bevacizumab is Safe and effective in the patient’s refractory to prior systemic therapy. However, when used as a second-line therapy, patients tend to have lower Median Odds of survival and Median progression-free survival. The outcome also changes with the type of prior systemic chemotherapy, with initial hyper-progression reported with prior therapy with lenvatinib. The AFP response at six weeks could be a predictive indicator of disease progression.

PR: Partial response, SR: Sustain response, CR: Complete response, PD: Progressive disease, mOS: median overall survival, mPFS: median Progression free survival.