ArticlePloS one2026
Comparison of outcomes of second-line durvalumab plus tremelimumab versus lenvatinib following first-line atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma.
Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
aimThe 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).
methodsIn 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.
resultsThe 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).
conclusionsAfter 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.
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