Lenvatinib versus Sorafenib as first-line treatment in hepatocellular carcinoma: A multi-institutional matched case-control study

Margherita Rimini; Shigeo Shimose; Sara Lonardi; Toshifumi Tada; Gianluca Masi; Hideki Iwamoto; Eleonora Lai; Valentina Burgio; Atsushi Hiraoka; Toru Ishikawa; Caterina Soldà; Tomotake Shirono; Caterina Vivaldi; Koichi Takaguchi; Noritomo Shimada; Giorgio Astara; Hironori Koga; Kazuhiro Nouso; Kouji Joko; Takuji Torimura; Yoichi Hiasa; Francesca Salani; Mario Scartozzi; Stefano Cascinu; Andrea Casadei-Gardini

doi:10.1111/hepr.13718

Lenvatinib versus Sorafenib as first-line treatment in hepatocellular carcinoma: A multi-institutional matched case-control study

Hepatol Res. 2021 Dec;51(12):1229-1241. doi: 10.1111/hepr.13718. Epub 2021 Oct 21.

Authors

Margherita Rimini¹, Shigeo Shimose², Sara Lonardi^{3

4}, Toshifumi Tada⁵, Gianluca Masi⁶, Hideki Iwamoto², Eleonora Lai⁷, Valentina Burgio⁸, Atsushi Hiraoka⁹, Toru Ishikawa¹⁰, Caterina Soldà⁴, Tomotake Shirono², Caterina Vivaldi⁶, Koichi Takaguchi¹¹, Noritomo Shimada¹², Giorgio Astara⁷, Hironori Koga², Kazuhiro Nouso¹³, Kouji Joko¹⁴, Takuji Torimura², Yoichi Hiasa¹⁵, Francesca Salani⁶, Mario Scartozzi⁷, Stefano Cascinu⁸, Andrea Casadei-Gardini⁸

Affiliations

¹ Division of Oncology, Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy.
² Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
³ Early Phase Clinical Trial Unit, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
⁴ Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
⁵ Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.
⁶ Unit of Medical Oncology, Pisa University Hospital, Pisa, Italy.
⁷ Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy.
⁸ Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy.
⁹ Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
¹⁰ Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
¹¹ Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
¹² Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.
¹³ Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
¹⁴ Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan.
¹⁵ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan.

PMID: 34591334
DOI: 10.1111/hepr.13718

Abstract

Background: Advanced Hepatocarcinoma (HCC) is an important health problem worldwide. Recently, the REFLECT trial demonstrated the non-inferiority of Lenvatinib compared to Sorafenib in I line setting, thus leading to the approval of new first-line standard of care, along with Sorafenib.

Aims and methods: With aim to evaluate the optimal choice between Sorafenib and Lenvatinib as primary treatment in clinical practice, we performed a multicentric analysis with the propensity score matching on 184 HCC patients.

Results: The median overall survival (OS) were 15.2 and 10.5 months for Lenvatinib and Sorafenib arm, respectively. The median progression-free survival (PFS) was 7.0 and 4.5 months for Lenvatinib and Sorafenib arm, respectively. Patients treated with Lenvatinib showed a 36% reduction of death risk (p = 0.0156), a 29% reduction of progression risk (p = 0.0446), a higher response rate (p < 0.00001) and a higher disease control rate (p = 0.002). Sorafenib showed to be correlated with more hand-foot skin reaction and Lenvatinib with more hypertension and fatigue. We highlighted the prognostic role of Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), bilirubin, alkaline phosphatase and eosinophils for Sorafenib. Conversely, albumin, aspartate aminotransferase (AST), alkaline phosphatase and Neutrophil-Lymphocyte Ratio (NLR) resulted prognostic in Lenvatinib arm. Finally, we highlighted the positive predictive role of albumin > Normal Value (NV), ECOG > 0, NLR < 3, absence of Hepatitis C Virus positivity, and presence of portal vein thrombosis in favor of Lenvatinib arm. Eosinophil < 50 and ECOG > 0 negatively predicted the response to Sorafenib.

Conclusion: SLenvatinib showed to better perform in a real-word setting compared to Sorafenib. More researches are needed to validate the predictor factors of response to Lenvatinib rather than Sorafenib.

Keywords: Lenvatinib; Sorafenib; hepatocarcinoma; prognostic and predictor factors.