Sorafenib as a second-line treatment after failure of atezolizumab-bevacizumab

Introduction Patients receiving atezolizumab/bevacizumab (AB) for HCC may have a primary resistance to this combination. Another relevant proportion of patients will develop secondary resistance and, eventually, experience progressive disease. Randomized clinical trials (RCTs) trying to identify second-line treatments are undergoing. If such trials are unavailable or patients are non-eligible, sorafenib is often prescribed based on European approval and reimbursement policies. However, evidence supporting these policies is lacking, as no RCTs explored sorafenib in this setting. Aim To assess the efficacy of sorafenib in patients who permanently stopped AB. Methods The ARTE database collects prospectively enrolled patients treated with AB in a real-life setting(March 2022-November 2023). We analysed the outcome of patients who received sorafenib as second-line treatment. Moreover, we performed a case-control matching with historical controls who had received sorafenib as a frontline treatment before AB had become available in clinical practice. Patients were matched 4:1, based on known predictors of overall survival (OS) in sorafenib-treated patients (Child-Pugh class, AFP>400ng/ml, macrovascular invasion, extrahepatic spread, ECOG-PS>0). Results Amongst the 157 patients included in the ARTE database, 130 (67.4%) permanently discontinued AB. Of them, 57 received a second-line treatment. Sorafenib was prescribed in 29 patients. The disease control rate (DCR) was 17.2%, with no objective responses. The median PFS and OS were 3.2 and 7.9 months. Compared with historical controls, patients who received sorafenib as a second-line therapy had worse DCR (17.1 vs 47.4%, p<0.01) and PFS. A trend toward a worse OS was also noted (Figure) Conclusions In the post-AB setting, we found a suboptimal efficacy outcome of sorafenib. The very low DCR suggests that resistance to AB might select tumour cells that are able to escape the therapeutic targets of sorafenib. Enrollment of these patients in RCTs is strongly recommended to identify better therapeutic strategies.