Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study.
Advanced HCC
Atezolizumab plus bevacizumab
First-line therapy
Lenvatinib
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
10
10
2022
accepted:
02
12
2022
medline:
23
10
2023
pubmed:
13
12
2022
entrez:
12
12
2022
Statut:
ppublish
Résumé
The purpose of this study is to compare response rates of lenvatinib and atezolizumab plus bevacizumab, in first-line real-world setting. Overall cohort included Western and Eastern hepatocellular carcinoma (HCC) patient populations from 46 centres in 4 countries (Italy, Germany, Japan, and Republic of Korea). 1312 patients were treated with lenvatinib, and 823 patients were treated with atezolizumab plus bevacizumab. Objective response rate (ORR) was 38.6% for patients receiving lenvatinib, and 27.3% for patients receiving atezolizumab plus bevacizumab (p < 0.01; odds ratio 0.60). For patients who achieved complete response (CR), overall survival (OS) was not reached in both arms, but the result from univariate Cox regression model showed 62% reduction of death risk for patients treated with atezolizumab plus bevacizumab (p = 0.05). In all multivariate analyses, treatment arm was not found to be an independent factor conditioning OS. Comparing ORR achieved in the two arms, there was a statistically significant difference in favor of lenvatinib compared to atezolizumab plus bevacizumab in all subgroups except for Eastern patients, Child-Pugh B patients, presence of portal vein thrombosis, α-feto-protein ≥ 400 ng/mL, presence of extrahepatic disease, albumin-bilirubin (ALBI) grade 2, and no previous locoregional procedures. Lenvatinib achieves higher ORR in all patient subgroups. Patients who achieve CR with atezolizumab plus bevacizumab can achieve OS so far never recorded in HCC patients. This study did not highlight any factors that could identify patient subgroups capable of obtaining CR.
Identifiants
pubmed: 36509984
doi: 10.1007/s00432-022-04512-1
pii: 10.1007/s00432-022-04512-1
doi:
Substances chimiques
atezolizumab
52CMI0WC3Y
Bevacizumab
2S9ZZM9Q9V
lenvatinib
EE083865G2
Types de publication
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5591-5602Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Burgio V, Iavarone M, Di Costanzo GG, Marra F, Lonardi S, Tamburini E et al (2021) Real-life clinical data of lenvatinib versus sorafenib for unresectable hepatocellular carcinoma in Italy. Cancer Manag Res 13:9379–9389
doi: 10.2147/CMAR.S330195
pubmed: 34992463
pmcid: 8713715
Casadei-Gardini A, Scartozzi M, Tada T, Yoo C, Shimose S, Masi G et al (2021) Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: an inverse probability of treatment weighting analysis. Liver Int 00:1–9
Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS et al (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10(1):25–34
doi: 10.1016/S1470-2045(08)70285-7
pubmed: 19095497
Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al (2022) Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol 76(4):862–873
doi: 10.1016/j.jhep.2021.11.030
pubmed: 34902530
Ducreux M, Zhu AX, Cheng A-L et al (2021) IMbrave150: Exploratory analysis to examine the association between treatment response and overall survival (OS) in patients (pts) with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor). J Clin Oncol 39(15):4071
doi: 10.1200/JCO.2021.39.15_suppl.4071
Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T-Y et al (2020) Complete responses (CR) in patients receiving atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in IMbrave150: a phase III clinical trial for unresectable hepatocellular carcinoma (HCC). J Clin Oncol 38(15):4596
doi: 10.1200/JCO.2020.38.15_suppl.4596
Freites-Martinez A, Santana N, Arias-Santiago S, Viera A (2021) Using the common terminology criteria for adverse events (CTCAE - Version 5.0) to evaluate the severity of adverse events of anticancer therapies. Actas Dermosifiliogr (Engl Ed) 112(1):90–92.
Han Y, Zhi WH, Xu F, Zhang CB, Huang XQ, Luo JF (2021) Selection of first-line systemic therapies for advanced hepatocellular carcinoma: a network meta-analysis of randomized controlled trials. World J Gastroenterol 27(19):2415–2433
doi: 10.3748/wjg.v27.i19.2415
pubmed: 34040331
pmcid: 8130040
Hatanaka T, Kakizaki S, Nagashima T, Namikawa M, Tojima H, Shimada Y et al (2020) Analyses of objective response rate, progression-free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: a multicenter retrospective study. Hepatol Res 50:382–395
doi: 10.1111/hepr.13460
pubmed: 31760660
Hiraoka A, Kumada T, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T et al (2019) Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions-multicenter analysis. Cancer Med 8:3719–3728
doi: 10.1002/cam4.2241
pubmed: 31127698
pmcid: 6639201
Iwamoto H, Shimose S, Noda Y, Shirono T, Niizeki T, Nakano M et al (2021) Initial experience of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in real-world clinical practice. Cancers 13:2786
doi: 10.3390/cancers13112786
pubmed: 34205099
pmcid: 8199943
Keenan BP, Fong L, Kelley RK (2019) Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response. J Immunother Cancer 7:1–13
doi: 10.1186/s40425-019-0749-z
Khoja L, Kibiro M, Metser U, Gedye C, Hogg D, Butler MO et al (2016) Patterns of response to anti-PD-1 treatment: an exploratory comparison of four radiological response criteria and associations with overall survival in metastatic melanoma patients. Br J Cancer 15:1186–1192
doi: 10.1038/bjc.2016.308
Kim BK, Cheon J, Kim H, Kang B, Ha Y, Kim DY et al (2022) Atezolizumab/bevacizumab vs. lenvatinib as first-line therapy for unresectable hepatocellular carcinoma: a real-world, multi-center study. Cancers 14:1747
doi: 10.3390/cancers14071747
pubmed: 35406518
pmcid: 8996911
Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F et al (2018) Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391(10126):1163–1173
doi: 10.1016/S0140-6736(18)30207-1
pubmed: 29433850
Kudo M, Finn RS, Qin S, Han K-H, Ikeda K, Cheng A-L et al (2019a) Analysis of survival and objective response (OR) in patients with hepatocellular carcinoma in a phase III study of lenvatinib (REFLECT). J Clin Oncol 37(4):186
doi: 10.1200/JCO.2019.37.4_suppl.186
Kudo M, Ueshima K, Chan S, Minami T, Chishina H, Aoki T et al (2019b) Lenvatinib as an initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and child–pugh A liver function: a proof-of-concept study. Cancers (basel) 11(8):1084
doi: 10.3390/cancers11081084
pubmed: 31370183
Liu JKH, Irvine AF, Jones RL, Samson A (2022) Immunotherapies for Hepatocellular Carcinoma. Cancer Med 11:571–591
doi: 10.1002/cam4.4468
pubmed: 34953051
Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338
doi: 10.1055/s-2007-1007122
pubmed: 10518312
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390
doi: 10.1056/NEJMoa0708857
pubmed: 18650514
Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S et al (2021) Hepatocellular Carcinoma. Nat Rev Dis Primers 7(1):6
doi: 10.1038/s41572-020-00240-3
pubmed: 33479224
Maruta S, Ogasawara S, Ooka Y, Obu M, Inoue M, Itokawa N et al (2020) Potential of lenvatinib for an expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma. Liver Cancer 9:382–396
doi: 10.1159/000507022
pubmed: 32999866
pmcid: 7506220
Ogushi K, Chuma M, Uojima H, Hidaka H, Numata K, Kobayashi S et al (2020) Safety and efficacy of lenvatinib treatment in Child-Pugh A and B patients with unresectable hepatocellular carcinoma in clinical practice: a multicenter analysis. Clin Exp Gastroenterol 13:385–396
doi: 10.2147/CEG.S256691
pubmed: 33061517
pmcid: 7534867
Ohki T, Sato K, Kondo M, Goto E, Sato T, Kondo Y et al (2020) Impact of adverse events on the progression-free survival of patients with advanced hepatocellular carcinoma treated with lenvatinib: a multicenter retrospective study. Drugs Real World Outcomes 7:141–149
doi: 10.1007/s40801-020-00179-7
pubmed: 32048238
pmcid: 7221074
Prieto J, Melero I, Sangro B (2015) Immunological landscape and immunotherapy of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 12:681–700
doi: 10.1038/nrgastro.2015.173
pubmed: 26484443
Rapposelli IG, De Matteis S, Lanuti P, Valgiusti M, Bartolini G, Ulivi P et al (2021a) Heterogeneity of response and immune system activity during treatment with nivolumab in hepatocellular carcinoma: results from a single-institution retrospective analysis. Cancers 13:213
doi: 10.3390/cancers13020213
pubmed: 33430142
pmcid: 7827490
Rapposelli IG, Tada T, Shimose S, Burgio V, Kumada T, Iwamoto H et al (2021b) Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib. Liver Int 41(12):2997–3008
doi: 10.1111/liv.15014
pubmed: 34250737
Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á et al (2022) BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol 76(3):681–693
doi: 10.1016/j.jhep.2021.11.018
pubmed: 34801630
Rimini M, Shimose S, Lonardi S, Tada T, Masi G, Iwamoto H et al (2021) Lenvatinib versus Sorafenib as first-line treatment in hepatocellular carcinoma: a multi-institutional matched case-control study. Hepatol Res 51(12):1229–1241
doi: 10.1111/hepr.13718
pubmed: 34591334
Rimini M, Liscia N, Burgio V, Casadei-Gardini A (2022) Why does survival of hepatocellular carcinoma patients remain so low? Key stumbling blocks and questions in preclinical and clinical development. Expert Opin Investig Drugs 31(5):483–494
doi: 10.1080/13543784.2022.2053108
pubmed: 35275784
Sasaki R, Fukushima M, Haraguchi M, Miuma S, Miyaaki H, Hidaka M et al (2019) Response to lenvatinib is associated with optimal relative dose intensity in hepatocellular carcinoma: experience in clinical settings. Cancers 11:1769
doi: 10.3390/cancers11111769
pubmed: 31717674
pmcid: 6895891
Shimose S, Kawaguchi T, Tanaka M, Iwamoto H, Miyazaki K, Moriyama E et al (2020) Lenvatinib prolongs the progression-free survival time of patients with intermediate-stage hepatocellular carcinoma refractory to transarterial chemoembolization: a multicenter cohort study using data mining analysis. Oncol Lett 20(3):2257–2265
doi: 10.3892/ol.2020.11758
pubmed: 32782543
pmcid: 7400966
Shimose S, Iwamoto H, Tanaka M, Niizeki T, Shirono T, Noda Y et al (2021) Alternating lenvatinib and trans-arterial therapy prolongs overall survival in patients with intermediate stage hepatocellular carcinoma: a propensity score matching study. Cancers 13:160
doi: 10.3390/cancers13010160
pubmed: 33466496
pmcid: 7796435
Sho T, Suda G, Ogawa K, Shigesawa T, Suzuki K, Nakamura A et al (2020) Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria. Hepatol Res 50:966–977
pubmed: 32562334
Sonbol MB, Riaz IB, Naqvi SAA (2020) Systemic therapy and sequencing options in advanced hepatocellular carcinoma: a systematic review and network meta-analysis. JAMA Oncol 6(12):e204930
doi: 10.1001/jamaoncol.2020.4930
pubmed: 33090186
pmcid: 7582230
Spallanzani A, Orsi G, Andrikou K, Gelsomino F, Rimini M, Riggi L et al (2018) Lenvatinib as a therapy for unresectable hepatocellular carcinoma. Expert Rev Anticancer Ther 18(11):1069–1076
doi: 10.1080/14737140.2018.1524297
pubmed: 30220234
Tazdait M, Mezquita L, Lahmar J, Ferrara R, Bidault F, Ammari S et al (2018) Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: comparison of RECIST 1.1, irRECIST and iRECIST criteria. Eur J Cancer 88:38–47
doi: 10.1016/j.ejca.2017.10.017
pubmed: 29182990
Ueshima K, Nishida N, Hagiwara S, Aoki T, Minami T, Chishina H et al (2019) Impact of baseline ALBI grade on the outcomes of hepatocellular carcinoma patients treated with lenvatinib: a multicenter study. Cancers 11:952
doi: 10.3390/cancers11070952
pubmed: 31284682
pmcid: 6678474
Wherry EJ (2011) T cell exhaustion. Nat Immunol 12:492–499
doi: 10.1038/ni.2035
pubmed: 21739672
Zambrana F, Carril-Ajuria L, Gómez de Liaño A, Martinez Chanza N, Manneh R, Castellano D et al (2021) Complete response and renal cell carcinoma in the immunotherapy era: the paradox of good news. Cancer Treat Rev 99:102239
doi: 10.1016/j.ctrv.2021.102239
pubmed: 34157582