Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib following Immunotherapy: A Real World Evidence Study

SIMPLE SUMMARY: Immunotherapy with atezolizumab plus bevacizumab as well as tremelimumab plus durvalumab has recently become the preferred first-line treatment for advanced hepatocellular carcinoma (HCC). Lenvatinib was initially approved as a first-line treatment, but little is known about its effectiveness following immunotherapy. The aim of our retrospective study was to characterize the clinical outcomes with lenvatinib following immunotherapy treatment. In our cohort of 53 patients, the median progression free survival was 3.7 months, and the median overall survival was 12.8 months from lenvatinib initiation. Multivariate analysis demonstrated race, gender, and Child Pugh Class as significant predictors of survival outcomes and BMI as well as distant metastasis as predictors of progression free survival. This study supports the efficacy of lenvatinib following immunotherapy and validates the use of lenvatinib as a second-line therapy following progression on immunotherapy in patients with advanced HCC. ABSTRACT: Background: Lenvatinib, a multikinase inhibitor, is an FDA-approved treatment for advanced hepatocellular carcinoma (HCC) in the first-line setting. Recent trial data have established atezolizumab plus bevacizumab as well as tremelimumab plus durvalumab as preferred first-line treatment options for advanced HCC. The role of lenvatinib following progression on immunotherapy in patients with advanced HCC remains unclear. Methods: We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010 and 2021 at the Mayo Clinic in Minnesota, Arizona, and Florida who received immunotherapy followed by lenvatinib. Median overall survival and progression-free survival analyses were performed using the Kaplan–Meier method, and responses were determined using RECIST 1.1. Adverse events were determined using CTCAE v 4.0. Results: We identified 53 patients with advanced HCC who received lenvatinib following progression on immunotherapy. Forty five (85%) patients had a Child Pugh class A at diagnosis, while 30 (58%) patients were still Child Pugh A at time of lenvatinib initiation. Lenvatinib was administered as a second-line treatment in 85% of the patients. The median PFS was 3.7 months (95% CI: 3.2–6.6), and the median OS from the time of lenvatinib initiation was 12.8 months (95% CI: 6.7–19.5). In patients with Child Pugh class A, the median OS and PFS was 14 and 5.2 months, respectively. Race, gender, and Child Pugh class was associated with OS on multivariate analysis. Discussion: Our study, using real-world data, suggests that patients benefit from treatment with lenvatinib following progression on immunotherapy in advanced HCC. The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown, and these results need to be validated in a clinical trial.