Introduction: In the REFLECT trial, lenvatinib was found to be noninferior compared to sorafenib in terms of overall survival. Here, we analyze the effects of lenvatinib in the real-life experience of several centers across the world and identify clinical factors that could be significantly associated with survival outcomes. Methods: The study population was derived from retrospectively collected data of HCC patients treated with lenvatinib. The overall cohort included western and eastern populations from 23 center in five countries. Results: We included 1,325 patients with HCC and treated with lenvatinib in our analysis. Median OS was 16.1 months. Overall response rate was 38.5%. Multivariate analysis for OS highlighted that HBsAg positive, NLR >3, and AST >38 were independently associated with poor prognosis in all models. Conversely, NAFLD/NASH-related etiology was independently associated with good prognosis. Median progression-free survival was 6.3 months. Multivariate analysis for progression-free survival revealed that NAFLD/NASH, BCLC, NLR, and AST were independent prognostic factors for progression-free survival. A proportion of 75.2% of patients suffered from at least one adverse effect during the study period. Multivariate analysis exhibited the appearance of decreased appetite grade ≥2 versus grade 0–1 as an independent prognostic factor for worse progression-free survival. 924 patients of 1,325 progressed during lenvatinib (69.7%), and 827 of them had a follow-up over 2 months from the beginning of second-line treatment. From first-line therapy, the longest median OS was obtained with the sequence lenvatinib and immunotherapy (47.0 months), followed by TACE (24.7 months), ramucirumab (21.2 months), sorafenib (15.7 months), regorafenib (12.7 months), and best supportive care (10.8 months). Conclusions: Our study confirms in a large and global population of patients with advanced HCC, not candidates for locoregional treatment the OS reported in the registration study and a high response rate with lenvatinib.

Real Life Study of Lenvatinib Therapy for Hepatocellular Carcinoma: RELEVANT Study / CASADEI GARDINI, Andrea; Rimini, Margherita; Kudo, Masatoshi; Shimose, Shigeo; Tada, Toshifumi; Suda, Goki; Ji Goh, Myung; Jefremow, Andre; Scartozzi, Mario; Cabibbo, Giuseppe; Campani, Claudia; Tamburini, Emiliano; Tovoli, Francesco; Ueshima, Kazuomi; Aoki, Tomoko; Iwamoto, Hideki; Torimura, Takuji; Kumada, Takashi; Hiraoka, Atsushi; Atsukawa, Masanori; Itobayashi, Ei; Toyoda, Hidenori; Sakamoto, Naoya; Sho, Takuya; Kang, Wonseok; Siebler, Jürgen; Friedrich Neurath, Markus; Burgio, Valentina; Cascinu, Stefano. - In: LIVER CANCER. - ISSN 2235-1795. - 11:6(2022), pp. 527-539. [10.1159/000525145]

Real Life Study of Lenvatinib Therapy for Hepatocellular Carcinoma: RELEVANT Study

Andrea Casadei-Gardini
Primo
;
Margherita Rimini
Secondo
;
Stefano Cascinu
Ultimo
2022-01-01

Abstract

Introduction: In the REFLECT trial, lenvatinib was found to be noninferior compared to sorafenib in terms of overall survival. Here, we analyze the effects of lenvatinib in the real-life experience of several centers across the world and identify clinical factors that could be significantly associated with survival outcomes. Methods: The study population was derived from retrospectively collected data of HCC patients treated with lenvatinib. The overall cohort included western and eastern populations from 23 center in five countries. Results: We included 1,325 patients with HCC and treated with lenvatinib in our analysis. Median OS was 16.1 months. Overall response rate was 38.5%. Multivariate analysis for OS highlighted that HBsAg positive, NLR >3, and AST >38 were independently associated with poor prognosis in all models. Conversely, NAFLD/NASH-related etiology was independently associated with good prognosis. Median progression-free survival was 6.3 months. Multivariate analysis for progression-free survival revealed that NAFLD/NASH, BCLC, NLR, and AST were independent prognostic factors for progression-free survival. A proportion of 75.2% of patients suffered from at least one adverse effect during the study period. Multivariate analysis exhibited the appearance of decreased appetite grade ≥2 versus grade 0–1 as an independent prognostic factor for worse progression-free survival. 924 patients of 1,325 progressed during lenvatinib (69.7%), and 827 of them had a follow-up over 2 months from the beginning of second-line treatment. From first-line therapy, the longest median OS was obtained with the sequence lenvatinib and immunotherapy (47.0 months), followed by TACE (24.7 months), ramucirumab (21.2 months), sorafenib (15.7 months), regorafenib (12.7 months), and best supportive care (10.8 months). Conclusions: Our study confirms in a large and global population of patients with advanced HCC, not candidates for locoregional treatment the OS reported in the registration study and a high response rate with lenvatinib.
2022
Hepatocellular carcinoma,Lenvatinib,ALBI,Neutrophils to lymphocyte ratio,Nonalcoholic steatohepatitis,Nonalcoholic fatty liver disease,Tyrosine kinase inhibitors,Outcome,Second line
File in questo prodotto:
File Dimensione Formato  
000525145.pdf

accesso aperto

Tipologia: PDF editoriale (versione pubblicata dall'editore)
Licenza: Creative commons
Dimensione 419.19 kB
Formato Adobe PDF
419.19 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/142836
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 11
social impact