Safety and Efficacy of Lenvatinib in Very Old Patients with Unresectable Hepatocellular Carcinoma.
Journal
Targeted oncology
ISSN: 1776-260X
Titre abrégé: Target Oncol
Pays: France
ID NLM: 101270595
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
accepted:
11
12
2023
medline:
1
2
2024
pubmed:
22
1
2024
entrez:
22
1
2024
Statut:
ppublish
Résumé
Data concerning the use of lenvatinib in very old patients (≥ 80 years) are limited, although the incidence of hepatocellular carcinoma (HCC) in this patient population is constantly increasing. This analysis aimed to evaluate the efficacy and safety of lenvatinib in a large cohort of very old patients (≥ 80 years) with unresectable HCC. The study was conducted on a cohort of 1325 patients from 46 centers in four Western and Eastern countries (Italy, Germany, Japan, and the Republic of Korea) who were undergoing first-line treatment with lenvatinib between July 2010 and February 2022. Patients were stratified according to age as very old (≥ 80 years) and not very old (< 80 years). The median overall survival (OS) was 15.7 months for patients < 80 years old and 18.4 months for patients ≥ 80 years old [hazard ratio (HR) = 1.02, 95% confidence interval (CI) 0.84-1.25, p = 0.8281]. Median progression free survival (PFS) was 6.3 months for patients < 80 years old and 6.5 months for patients ≥ 80 years old (HR = 1.07, 95% CI 0.91-1.25, p = 0.3954). No differences between the two study groups were found in terms of disease control rate (DCR; 80.8% versus 78.8%; p = 0.44) and response rate (RR; 38.2% versus 37.9%; p = 0.88). Patients < 80 years old experienced significantly more hand-foot skin reaction (HFSR) grade ≥ 2 and decreased appetite grade ≥ 2. Conversely, patients ≥ 80 years old experienced significantly more fatigue grade ≥ 2. In the very old group, parameters associated with prognosis were AFP, albumin-bilirubin (ALBI) grade, Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh score. BCLC stage was the only independent predictor of overall survival (OS; HR = 1.59, 95% CI 1.11-2.29, p = 0.01115). Our study highlights the same efficacy and safety of lenvatinib between very old and not very old patients.
Sections du résumé
BACKGROUND
BACKGROUND
Data concerning the use of lenvatinib in very old patients (≥ 80 years) are limited, although the incidence of hepatocellular carcinoma (HCC) in this patient population is constantly increasing.
OBJECTIVE
OBJECTIVE
This analysis aimed to evaluate the efficacy and safety of lenvatinib in a large cohort of very old patients (≥ 80 years) with unresectable HCC.
PATIENTS AND METHODS
METHODS
The study was conducted on a cohort of 1325 patients from 46 centers in four Western and Eastern countries (Italy, Germany, Japan, and the Republic of Korea) who were undergoing first-line treatment with lenvatinib between July 2010 and February 2022. Patients were stratified according to age as very old (≥ 80 years) and not very old (< 80 years).
RESULTS
RESULTS
The median overall survival (OS) was 15.7 months for patients < 80 years old and 18.4 months for patients ≥ 80 years old [hazard ratio (HR) = 1.02, 95% confidence interval (CI) 0.84-1.25, p = 0.8281]. Median progression free survival (PFS) was 6.3 months for patients < 80 years old and 6.5 months for patients ≥ 80 years old (HR = 1.07, 95% CI 0.91-1.25, p = 0.3954). No differences between the two study groups were found in terms of disease control rate (DCR; 80.8% versus 78.8%; p = 0.44) and response rate (RR; 38.2% versus 37.9%; p = 0.88). Patients < 80 years old experienced significantly more hand-foot skin reaction (HFSR) grade ≥ 2 and decreased appetite grade ≥ 2. Conversely, patients ≥ 80 years old experienced significantly more fatigue grade ≥ 2. In the very old group, parameters associated with prognosis were AFP, albumin-bilirubin (ALBI) grade, Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh score. BCLC stage was the only independent predictor of overall survival (OS; HR = 1.59, 95% CI 1.11-2.29, p = 0.01115).
CONCLUSIONS
CONCLUSIONS
Our study highlights the same efficacy and safety of lenvatinib between very old and not very old patients.
Identifiants
pubmed: 38252195
doi: 10.1007/s11523-023-01029-6
pii: 10.1007/s11523-023-01029-6
doi:
Substances chimiques
lenvatinib
EE083865G2
Phenylurea Compounds
0
Quinolines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
29-39Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660 .
doi: 10.3322/caac.21660
pubmed: 33538338
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90. https://doi.org/10.1056/NEJMoa0708857 .
doi: 10.1056/NEJMoa0708857
pubmed: 18650514
Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. 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. 2009;10(1):25–34. https://doi.org/10.1016/S1470-2045(08)70285-7 .
doi: 10.1016/S1470-2045(08)70285-7
pubmed: 19095497
Bruix J, Cheng AL, Meinhardt G, Nakajima K, De Sanctis Y, Llovet J. Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: analysis of two phase III studies. J Hepatol. 2017;67:999–1008. https://doi.org/10.1016/j.jhep.2017.06.026 .
doi: 10.1016/j.jhep.2017.06.026
pubmed: 28687477
Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–73. https://doi.org/10.1016/S0140-6736(18)30207-1 .
doi: 10.1016/S0140-6736(18)30207-1
pubmed: 29433850
Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022;76(4):862–73. https://doi.org/10.1016/j.jhep.2021.11.030 .
doi: 10.1016/j.jhep.2021.11.030
pubmed: 34902530
Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022. https://doi.org/10.1056/EVIDoa2100070 .
doi: 10.1056/EVIDoa2100070
Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66. https://doi.org/10.1016/S0140-6736(16)32453-9 .
doi: 10.1016/S0140-6736(16)32453-9
pubmed: 27932229
Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63. https://doi.org/10.1056/NEJMoa1717002 .
doi: 10.1056/NEJMoa1717002
pubmed: 29972759
pmcid: 7523244
Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282–96. https://doi.org/10.1016/S1470-2045(18)30937-9 .
doi: 10.1016/S1470-2045(18)30937-9
pubmed: 30665869
Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341(27):2061–7. https://doi.org/10.1056/NEJM199912303412706 .
doi: 10.1056/NEJM199912303412706
pubmed: 10615079
Tada T, Kumada T, Hiraoka A, Michitaka K, Atsukawa M, Hirooka M, et al. Safety and efficacy of lenvatinib in elderly patients with unresectable hepatocellular carcinoma: a multicenter analysis with propensity score matching. Hepatol Res. 2020;50(1):75–83. https://doi.org/10.1111/hepr.13427 .
doi: 10.1111/hepr.13427
pubmed: 31660700
Freites-Martinez A, Santana N, Arias-Santiago S, Viera A. 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). 2021;112(1):90–2.
doi: 10.1016/j.ad.2019.05.009
pubmed: 32891586
Decoster L, van Puyvelde SK, Mohile U, Wedding U, Basso G, Colloca S, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations. Ann Oncol. 2015;26:288–300. https://doi.org/10.1093/annonc/mdu210 .
doi: 10.1093/annonc/mdu210
pubmed: 24936581
Hajiev S, Allara E, Motedayen Aval L, Arizumi T, Bettinger D, Pirisi M, et al. Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study. Br J Cancer. 2021;124(2):407–13. https://doi.org/10.1038/s41416-020-01116-9 .
doi: 10.1038/s41416-020-01116-9
pubmed: 33071284
Zhang D, Wang X, Zhang M, Yin Y, Guo J. Clinical efficacy of chemotherapy in colorectal cancer patients over 80 years old. Int J Colorectal Dis. 2022;37(8):1853–63. https://doi.org/10.1007/s00384-022-04222-7 .
doi: 10.1007/s00384-022-04222-7
pubmed: 35857106
pmcid: 9388411
Owonikoko TK, Ragin CC, Belani CP, Oton AB, Gooding WE, Taioli E, et al. Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol. 2007;25(35):5570–7. https://doi.org/10.1200/JCO.2007.12.5435 .
doi: 10.1200/JCO.2007.12.5435
pubmed: 18065729
Shachar SS, Hurria A, Muss HB. Breast cancer in women older than 80 years. J Oncol Pract. 2016;12(2):123–32. https://doi.org/10.1200/JOP.2015.010207 .
doi: 10.1200/JOP.2015.010207
pubmed: 26869650
Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Real-life Practice Experts for HCC (RELPEC) Study Group and the Hepatocellular Carcinoma Experts from 48 clinics in Japan (HCC 48) Group, et al. Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: a multicenter analysis. Cancer Med. 2022;11(20):3796–808. https://doi.org/10.1002/cam4.4763 .
doi: 10.1002/cam4.4763
pubmed: 35441477
pmcid: 9582693
Vithayathil M, D’Alessio A, Fulgenzi CAM, Nishida N, Schönlein M, von Felden J, et al. Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Liver Int. 2022;42(11):2538–47. https://doi.org/10.1111/liv.15405 .
doi: 10.1111/liv.15405
pubmed: 35986902
pmcid: 9825835
Rimini M, Rimassa L, Ueshima K, Burgio V, Shigeo S, Tada T, et al. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis. ESMO Open. 2022;7(6): 100591. https://doi.org/10.1016/j.esmoop.2022.100591 .
doi: 10.1016/j.esmoop.2022.100591
pubmed: 36208496
pmcid: 9808460
Casadei-Gardini A, Rimini M, Tada T, Suda G, Shimose S, Kudo M, et al. Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Eur J Cancer. 2023;180:9–20. https://doi.org/10.1016/j.ejca.2022.11.017 .
doi: 10.1016/j.ejca.2022.11.017
pubmed: 36527976
Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen ML, Extermann M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32(24):2595–603. https://doi.org/10.1200/JCO.2013.54.8347 .
doi: 10.1200/JCO.2013.54.8347
pubmed: 25071125
pmcid: 4876338
Mohile SG, Dale W, Somerfield MR, Hurria A. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO Guideline for Geriatric Oncology Summary. J Oncol Pract. 2018;14(7):442–6. https://doi.org/10.1200/JOP.18.00180 .
doi: 10.1200/JOP.18.00180
pubmed: 29932846
Dotan E, Walter LC, Browner IS, Clifton K, Cohen HJ, Extermann M, et al. NCCN Guidelines
doi: 10.6004/jnccn.2021.0043
Alexander K, Korc-Grodzicki B. Comprehensive geriatric assessment (CGA) for cancer patients. In: Extermann M, editor. Geriatric oncology. Cham: Springer International Publishing; 2018. p. 1–14.
Bruijnen CP, Heijmer A, van Harten-Krouwel DG, van den Bos F, de Bree R, Witteveen PO, et al. Validation of the G8 screening tool in older patients with cancer considered for surgical treatment. J Geriatr Oncol. 2021;12(5):793–8. https://doi.org/10.1016/j.jgo.2020.10.017 .
doi: 10.1016/j.jgo.2020.10.017
pubmed: 33172806
Socha K, Sołtysik BK, Cieślak-Skubel A, Piechocka-Wochniak E, Błaszczak R, Kostka T. Validation of the Vulnerable Elders Survey-13 (VES-13) in hospitalized older patients. Eur Geriatr Med. 2016;7(5):449–53. https://doi.org/10.1016/j.eurger.2016.03.008 .
doi: 10.1016/j.eurger.2016.03.008
Yang CJ, Brown AB, Deng JZ, Lui NS, Backhus LM, Shrager JB, et al. The oldest old: a national analysis of outcomes for patients 90 years or older with lung cancer. Ann Thorac Surg. 2020;109(2):350–7. https://doi.org/10.1016/j.athoracsur.2019.09.027 .
doi: 10.1016/j.athoracsur.2019.09.027
pubmed: 31757356
Nakayama Y, Kawamura H, Honda M, Takano Y, Takiguchi K, Kamiga T, et al. Benefit of intensive chemotherapy for elderly patients aged 80 years or older with metastatic colorectal cancer: a state-wide multicenter cohort study. Int J Clin Oncol. 2021;26(7):1248–56. https://doi.org/10.1007/s10147-021-01909-9 .
doi: 10.1007/s10147-021-01909-9
pubmed: 34089402
Takahashi A, Moriguchi M, Seko Y, Ishikawa H, Yo T, Kimura H, et al. Impact of relative dose intensity of early-phase lenvatinib treatment on therapeutic response in hepatocellular carcinoma. Anticancer Res. 2019;39(9):5149–56. https://doi.org/10.21873/anticanres.13710 .
doi: 10.21873/anticanres.13710
pubmed: 31519627
Chan LL, Mo FKF, Law ALY, Shum TCY, Tai AYP, Lee A-S, et al. Impact of dose adjustment on clinical outcomes of lenvatinib-treated patients with advanced hepatocellular carcinoma (HCC). Poster presented at: 16th Annual International Liver Cancer Association Conference, September 1–4, 2022, Madrid. Accessed September 7, 2022.
Welland S, Leyh C, Finkelmeier F, Jefremow A, Shmanko K, Gonzalez-Carmona MA, et al. Real-world data for lenvatinib in hepatocellular carcinoma (ELEVATOR): a retrospective multicenter study. Liver Cancer. 2022;11(3):219–32. https://doi.org/10.1159/000521746 .
doi: 10.1159/000521746
pubmed: 35949288
pmcid: 9218621
Casadei-Gardini A, Rimini M, Kudo M, Shimose S, Tada T, Suda G, et al. Real life study of lenvatinib therapy for hepatocellular carcinoma: RELEVANT study. Liver Cancer. 2022;11(6):527–39. https://doi.org/10.1159/000525145 .
doi: 10.1159/000525145
pubmed: 36589723
pmcid: 9801178
Burgio V, Iavarone M, Di Costanzo GG, Marra F, Lonardi S, Tamburini E, et al. Real-life clinical data of lenvatinib versus sorafenib for unresectable hepatocellular carcinoma in Italy. Cancer Manag Res. 2021;13:9379–89. https://doi.org/10.2147/CMAR.S330195 .
doi: 10.2147/CMAR.S330195
pubmed: 34992463
pmcid: 8713715
Rimini M, Shimose S, Lonardi S, Tada T, Masi G, Iwamoto H, et al. Lenvatinib versus sorafenib as first-line treatment in hepatocellular carcinoma: a multi-institutional matched case-control study. Hepatol Res. 2021;51(12):1229–41. https://doi.org/10.1111/hepr.13718 .
doi: 10.1111/hepr.13718
pubmed: 34591334
Llovet JM, Kudo M, Merle P, Meyer T, Qin S, Ikeda M, LEAP-002 Investigators, et al. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24(12):1399–410. https://doi.org/10.1016/S1470-2045(23)00469-2 .
doi: 10.1016/S1470-2045(23)00469-2
pubmed: 38039993
Rao AV, Cohen HJ. Fatigue in older cancer patients: etiology, assessment, and treatment. Semin Oncol. 2008;35(6):633–42. https://doi.org/10.1053/j.seminoncol.2008.08.005 .
doi: 10.1053/j.seminoncol.2008.08.005
pubmed: 19027467
Okubo H, Ando H, Ishizuka K, Kitagawa R, Okubo S, Saito H, et al. Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma. PLoS One. 2020;15(3): e0229772. https://doi.org/10.1371/journal.pone.0229772 .
doi: 10.1371/journal.pone.0229772
pubmed: 32126131
pmcid: 7053710
Hiraoka A, Kumada T, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T, et al. Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions—multicenter analysis. Cancer Med. 2019;8(8):3719–28. https://doi.org/10.1002/cam4.2241 .
doi: 10.1002/cam4.2241
pubmed: 31127698
pmcid: 6639201
Casadei-Gardini A, Scartozzi M, Tada T, Yoo C, Shimose S, Masi G, et al. Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: an inverse probability of treatment weighting analysis. Liver Int. 2021;41(6):1389–97.
doi: 10.1111/liv.14817
pubmed: 33547848
Rimini M, Kudo M, Tada T, Shigeo S, Kang W, Suda G, et al. Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib. ESMO Open. 2021;6(6): 100330.
doi: 10.1016/j.esmoop.2021.100330
pubmed: 34847382
pmcid: 8710492
Rapposelli IG, Shimose S, Kumada T, Okamura S, Hiraoka A, Di Costanzo GG, et al. Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma. ESMO Open. 2021;6(4): 100190. https://doi.org/10.1016/j.esmoop.2021.100190 .
doi: 10.1016/j.esmoop.2021.100190
pubmed: 34144271
pmcid: 8219999
Alsina A, Kudo M, Vogel A, Cheng AL, Tak WY, Ryoo BY, et al. Effects of subsequent systemic anticancer medication following first-line lenvatinib: a post hoc responder analysis from the phase 3 REFLECT Study in unresectable hepatocellular carcinoma. Liver Cancer. 2020;9(1):93–104. https://doi.org/10.1159/000504624 .
doi: 10.1159/000504624
pubmed: 32071913
Hiraoka A, Kumada T, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T, Real-life practice experts for HCC (RELPEC) Study Group, HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan), et al. Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions—multicenter analysis. Cancer Med. 2019;8(8):3719–28. https://doi.org/10.1002/cam4.2241 .
doi: 10.1002/cam4.2241
pubmed: 31127698
pmcid: 6639201
Vogel A, Qin S, Kudo M, Su Y, Hudgens S, Yamashita T, et al. Lenvatinib versus sorafenib for first-line treatment of unresectable hepatocellular carcinoma: patient-reported outcomes from a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2021;6(8):649–58. https://doi.org/10.1016/S2468-1253(21)00110-2 .
doi: 10.1016/S2468-1253(21)00110-2
pubmed: 34087115