Comparison of outcomes of second-line durvalumab plus tremelimumab versus lenvatinib following first-line atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma.

Abstract

The optimal second-line therapy following first-line atezolizumab plus bevacizumab remains unascertained. In this study, we compared second-line durvalumab plus tremelimumab with lenvatinib after first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma (uHCC). In this retrospective, open-label, non-randomized comparative study, we analyzed real-world data derived from a prospectively registered observational cohort of patients with uHCC who received durvalumab plus tremelimumab (the Dur/Tre group, n = 14) or lenvatinib (the Len group, n = 67) as second-line therapy after first-line atezolizumab plus bevacizumab. Tumor response was assessed using the RECIST criteria version 1.1. Progression-free survival (PFS), overall survival (OS), adverse events (AEs), and changes in the albumin-bilirubin (ALBI) score were compared between the groups. The objective response and disease control rates were 7.7% and 15.4% in the Dur/Tre group and 23.3% and 76.7% in the Len group, respectively. The median PFS was 1.7 vs. 4.2 months (p < 0.001) and median OS was 5.3 vs. 14.0 months (p = 0.047) in the Dur/Tre and Len groups, both significantly favoring lenvatinib. Multivariable analysis showed that lenvatinib treatment was an independent predictor of longer PFS, and a neutrophil-to-lymphocyte ratio ≥ 3 was an independent predictor of worse OS. Grade ≥ 3 AEs were more frequent with lenvatinib than with durvalumab plus tremelimumab (70.1% vs. 21.4%; p = 0.002). At week 4, the ALBI score was maintained with durvalumab plus tremelimumab (-2.30 to -2.21; p = 0.318) but worsened with lenvatinib (-2.36 to -1.97; p < 0.001). After first-line atezolizumab plus bevacizumab, second-line lenvatinib achieved superior disease control and longer survival than durvalumab plus tremelimumab. However, grade ≥ 3 AEs were more frequent with lenvatinib than with durvalumab plus tremelimumab. Careful AE management is therefore important when selecting therapy for individual patients.