Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A Retrospective Multicenter Study

Sabrina Welland; Catherine Leyh; Fabian Finkelmeier; André Jefremow; Kateryna Shmanko; Maria A Gonzalez-Carmona; Arne Kandulski; Petia Jeliazkova; Jan Best; Thorben W Fründt; Angela Djanani; Maria Pangerl; Andreas Maieron; Richard Greil; Christina Fricke; Disorn Sookthai; Rainer Günther; Andreas Schmiderer; Henning Wege; Marino Venerito; Ursula Ehmer; Martina Müller; Christian P Strassburg; Arndt Weinmann; Jürgen Siebler; Oliver Waidmann; Christian M Lange; Anna Saborowski; Arndt Vogel

doi:10.1159/000521746

Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A Retrospective Multicenter Study

Liver Cancer. 2022 Jan 14;11(3):219-232. doi: 10.1159/000521746. eCollection 2022 Jun.

Authors

Sabrina Welland¹, Catherine Leyh², Fabian Finkelmeier³, André Jefremow^{4

5}, Kateryna Shmanko⁶, Maria A Gonzalez-Carmona⁷, Arne Kandulski⁸, Petia Jeliazkova⁹, Jan Best¹⁰, Thorben W Fründt¹¹, Angela Djanani¹², Maria Pangerl¹³, Andreas Maieron¹⁴, Richard Greil¹⁵, Christina Fricke¹⁴, Disorn Sookthai¹⁶, Rainer Günther¹³, Andreas Schmiderer¹², Henning Wege¹¹, Marino Venerito¹⁷, Ursula Ehmer⁹, Martina Müller⁸, Christian P Strassburg⁷, Arndt Weinmann⁶, Jürgen Siebler^{5

18}, Oliver Waidmann³, Christian M Lange², Anna Saborowski¹, Arndt Vogel¹

Affiliations

¹ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
² Department of Gastroenterology and Hepatology, University Hospital and University of Duisburg-Essen, Essen, Germany.
³ Department of Internal Medicine 1, Goethe-University Hospital Frankfurt, Frankfurt, Germany.
⁴ Department of Internal Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
⁵ CCC-Erlangen EMN, Erlangen, Germany.
⁶ Department of Medicine I, University Medical Center Johannes Gutenberg University, Mainz, Germany.
⁷ Department of Internal Medicine 1, University Hospital of Bonn, Bonn, Germany.
⁸ Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
⁹ Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
¹⁰ Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
¹¹ Department of Gastroenterology and Hepatology, University Medical Center, Hamburg, Germany.
¹² Department of Gastroenterology, Hepatology and Endocrinology, University Hospital of Innsbruck, Innsbruck, Austria.
¹³ Department of Internal Medicine I, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany.
¹⁴ Internal Medicine 2, Gastroenterology and Hepatology and Rheumatology, Karl Landsteiner University of Health Sciences, University Hospital of St. Pölten, St. Pölten, Austria.
¹⁵ Salzburg Cancer Research Institute, Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectiology and Rheumatology, Oncologic Center, Erlangen, Germany.
¹⁶ Institut für Klinische Krebsforschung IKF GmbH, Frankfurt, Germany.
¹⁷ Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University Hospital Magdeburg, Magdeburg, Germany.
¹⁸ Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.

Abstract

Background: Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria.

Methods: A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed.

Results: Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC.

Conclusion: Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

Keywords: Albumin-bilirubin grade; Hepatocellular carcinoma; Lenvatinib; Liver function; REFLECT study; Real-world cohort.