ALBI Grade Determines Post-progression Survivals after Sorafenib Treatment Failure in Advanced HCC Patients: A Model for Second-Line Trial Selection

Abstract

Introduction: Sorafenib can improve the overall survival (OS) and progression-free survival (PFS) of advanced hepatocellular carcinoma (HCC). Appropriate criteria for selection patients who can be enrolled in second-line trials are in unmet need. In this study, we aimed to evaluate the post-progression survival (PPS) in patients undergoing sorafenib for advanced HCC based on Albumin-Bilirubin (ALBI) grade, a new model with good performance in predicting OS of HCC. Methods: Consecutive 276 advanced HCC patients receiving sorafenib were retrospectively enrolled. All patients were in Child-Pugh A status and BCLC stage C with either portal vein invasion or extrahepatic metastasis. Radiologic evaluation was based on mRECIST criteria, clinical and compliance assessments were performed every two months, and two to four weeks, respectively. Results: During the median follow-up period of 5.6 months (interquartile range [IQR], 3.0-13.5), 220 (79.7%) patients developed progressive disease (PD) and 245 (88.8%) deaths occurred. The mean sorafenib dosage was 613.3mg (standard deviation, 189.7mg) per day; and the medium treatment duration was 64 days (IQR, 50-125). The median PFS, OS, and PPS were 2.1 (IQR, 1.4-5.9), 5.7 (IQR, 3.1-13.6), and 4.0 (IQR, 1.9-9.1) months, respectively. The ALBI grade could independently predict the OS (hazard ratio [HR], 1.505 for grade 2 vs 1; and 4.354 for grade 3 vs 1) but did not have a role in predicting PFS. Independent predictors of PPS included ALBI grade at progression (HR, 1.654 for grade 2 vs 1; and 2.655 for grade 3 vs 1), new extrahepatic lesions (NEH) (HR, 2.026), high alpha-fetoprotein level (HR, 1.801), and early progression within 4 months (HR, 1.591). In the subgroup analysis according to the alpha-fetoprotein level at PD and time to progression interval, better PPS was only presented while NEH(-), ALBI grade 1 in early PD, high AFP group as well as NEH(-), ALBI grade 1-2 in late PD, low AFP group. Conclusion: Liver function and progression pattern are important determinants of survival after sorafenib failure. The presence of NEH is contraindicated for second-line trials as a poor PPS can be expected. Patients with early PD and high AFP level, ALBI grade 1; or patients without early PD or high AFP level, ALBI grade 1 & 2 can be a new inclusion criteria of second-line trials for advanced HCC.