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

Background and AimThe optimal second-line therapy following first-line atezolizumab plus bevacizumab (Atezo/Beva) remains unascertained. This study compared second-line durvalumab plus tremelimumab (Dur/Tre) with lenvatinib (Len) after first-line Atezo/Beva in unresectable hepatocellular carcinoma (uHCC). MethodsThis prospectively registered cohort study analyzed patients with uHCC who received Dur/Tre (n = 14) or Len (n = 67) as second-line therapy after first-line Atezo/Beva. Tumor response was assessed by RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), adverse events (AEs), and changes in the albumin-bilirubin (ALBI) score were compared. ResultsThe objective response rate and disease control rate were 7.7% and 15.4% in the Dur/Tre group, and 23.3% and 76.7% in the Len group, respectively; 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 Len. Multivariable analysis showed that Len treatment and neutrophil-to-lymphocyte ratio [&ge;]3 were independent predictors of longer PFS and worse OS, respectively. Grade [&ge;]3 AEs were more frequent with Len than with Dur/Tre (70.1% vs. 21.4%; p = 0.002). At week 4, the ALBI score did not worsen with Dur/Tre (-2.30 to -2.21; p = 0.318) but worsened with Len (-2.36 to -1.97; p < 0.001). ConclusionsAfter first-line Atezo/Beva, second-line Len achieved superior disease control and longer survival than Dur/Tre. However, grade [&ge;] 3 AEs were more frequent with Len than with Dur/Tre, and careful management of AEs is essential when choosing therapy for individual patients.