Outcome of receiving lenvatinib following immunotherapy in patients with advanced hepatocellular carcinoma.

507 Background: Lenvatinib, a multikinase inhibitor, is an FDA approved treatment for advanced hepatocellular carcinoma (HCC) in the first line setting. Atezolizumab and bevacizumab are considered new standard of care as first line therapy after results of the IMBrave 150 trial. Currently, we do not have data to suggest any second-line treatment after administration of immunotherapy. We describe the clinical outcomes in patients with advanced HCC who received lenvatinib following treatment with immunotherapy. Methods: We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010 and 2021 at Mayo Clinic in Minnesota, Arizona, and Florida. The study was reviewed and approved by the intuitional review board. The primary outcomes were overall survival (OS) and progression free survival (PFS). Results: We identified 53 patients with advanced HCC who received lenvatinib following immunotherapy. Most patients (83%) were male. Median age at start of lenvatinib was 67 years old. Forty-two (79%) patients had a Child-Pugh score of A at diagnosis while 30 (58%) patients were still Child-Pugh A at time of lenvatinib initiation. Risk factors for HCC included Hep C (43%), alcohol use (34%), NASH (15%) and hepatitis B (7%). Forty-five (85%) patients received lenvatinib in the 2 nd line and 8 (15%) patients received it as third line or later. At time of data extraction, 38 (72%) patients had died. Median PFS was 4 months (95% CI: 3 – 6) and median OS from time of lenvatinib initiation was 13 months (95% CI: 6 – 24). The most common adverse events of any grade included fatigue (53%), hypertension (37%), AST elevation (30%), anorexia (28%), bilirubin elevation (25%) and diarrhea (25%). Twenty-one (40%) patients experienced grade 3 or higher adverse events including hypertension (25%), confusion (6%), acute kidney injury (2%), hyperkalemia (2%), ALT elevation (2%), proteinuria (2%), arthralgia (2%), heart failure (2%), AST elevation (2%), bilirubin elevation (2%), palmar-plantar erythrodysesthesia (2%), oral mucositis (2%), weight loss (2%), hypothyroidism (2%), anorexia (2%), fatigue (2%) and diarrhea (2%). Seven patients stopped treatment due to adverse events: 1 for hypertension, 2 for confusion, 1 for heart failure, 2 for fatigue, and 1 for elevated bilirubin. Conclusions: The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown. We found that median OS was 13 months in patients who received lenvatinib after immunotherapy which is comparable to survival in other studies when used as first line therapy. Our experience demonstrates that patients may benefit from treatment with lenvatinib following initial progression on immunotherapy.