Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial
Open accessAbstract
Background Systemic therapies have improved the management of hepatocellular carcinoma, but there is still a need to further enhance overall survival in first-line advanced stages. This study aimed to evaluate the addition of pembrolizumab to lenvatinib versus lenvatinib plus placebo in the first-line setting for unresectable hepatocellular carcinoma.Methods In this global, randomised, double-blind, phase 3 study (LEAP-002), patients aged 18 years or older with unresectable hepatocellular carcinoma, Child Pugh class A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no previous systemic treatment were enrolled at 172 global sites. Patients were randomly assigned (1:1) with a central interactive voice-response system (block size of 4) to receive lenvatinib (bodyweight <60 kg, 8 mg/day; bodyweight ≥60 kg, 12 mg/day) plus pembrolizumab (200 mg every 3 weeks) or lenvatinib plus placebo. Randomisation was stratified by geographical region, macrovascular portal vein invasion or extrahepatic spread or both, α-fetoprotein concentration, and Eastern Cooperative Oncology Group performance status. Dual primary endpoints were overall survival (superiority threshold at final overall survival analysis, one-sided p=0·019; final analysis to occur after 532 events) and progression-free survival (superiority threshold one-sided p=0·002; final analysis to occur after 571 events) in the intention-to-treat population. Results from the final analysis are reported. This study is registered with ClinicalTrials.gov, NCT03713593, and is active but not recruiting.Findings Between Jan 17, 2019, and April 28, 2020, of 1309 patients assessed, 794 were randomly assigned to lenvatinib plus pembrolizumab (n=395) or lenvatinib plus placebo (n=399). Median age was 66·0 years (IQR 57·0-72·0), 644 (81%) of 794 were male, 150 (19%) were female, 345 (43%) were Asian, 345 (43%) were White, 22 (3%) were multiple races, 21 (3%) were American Indian or Alaska Native, 21 (3%) were Native Hawaiian or other Pacific Islander, 13 (2%) were Black or African American, and 46 (6%) did not have available race data. Median follow up as of data cutoff for the final analysis (June 21, 2022) was 32·1 months (IQR 29·4-35·3). Median overall survival was 21·2 months (95% CI 19·0-23·6; 252 [64%] of 395 died) with lenvatinib plus pembrolizumab versus 19·0 months (17·2-21·7; 282 [71%] of 399 died) with lenvatinib plus placebo (hazard ratio [HR] 0·84; 95% CI 0·71-1·00; stratified log-rank p=0·023). As of data cutoff for the progression-free survival final analysis (April 5, 2021), median progression-free survival was 8·2 months (95% CI 6·4-8·4; 270 events occurred [42 deaths; 228 progressions]) with lenvatinib plus pembrolizumab versus 8·0 months (6·3-8·2; 301 events occurred [36 deaths; 265 progressions]) with lenvatinib plus placebo (HR 0·87; 95% CI 0·73-1·02; stratified log-rank p=0·047). The most common treatment-related grade 3-4 adverse events were hypertension (69 [17%] of 395 patients in the lenvatinib plus pembrolizumab group vs 68 [17%] of 395 patients) in the lenvatinib plus placebo group), increased aspartate aminotransferase (27 [7%] vs 17 [4%]), and diarrhoea (25 [6%] vs 15 [4%]). Treatment-related deaths occurred in four (1%) patients in the lenvatinib plus pembrolizumab group (due to gastrointestinal haemorrhage and hepatorenal syndrome [n=1 each] and hepatic encephalopathy [n=2]) and in three (1%) patients in the lenvatinib plus placebo group (due to gastrointestinal haemorrhage, hepatorenal syndrome, and cerebrovascular accident [n=1 each]).Interpretation In earlier studies, the addition of pembrolizumab to lenvatinib as first-line therapy for advanced hepatocellular carcinoma has shown promising clinical activity; however, lenvatinib plus pembrolizumab did not meet prespecified significance for improved overall survival and progression-free survival versus lenvatinib plus placebo. Our findings do not support a change in clinical practice.Funding Eisai US, and Merck Sharp & Dohme, a subsidiary of Merck.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Further stratification of non-viral etiologies was only done in COSMIC-312 and LEAP-002.
“Further stratification of non-viral etiologies was only done in COSMIC-312 and LEAP-002”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [36]
The Statistical Analysis section (page unavailable) lists viral aetiology as a yes-or-no subgroup but does not subdivide non-viral aetiologies; it also says that no additional subgroups were included post hoc. That is contrary to the claim that LEAP-002 further stratified non-viral aetiologies. This paper does not establish which other trials did so. (LLM, conf=0.78)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn LEAP-002, OS HR for non-viral HCC was 0.86 (0.66-1.13).
“In LEAP-002, outcomes for patients with viral and non-viral HCCs were similar, with HRs for OS being 0.84 (0.67–1.05) and 0.86 (0.66–1.13), respectively [36].”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [36]
The Statistical Analysis section identifies viral aetiology (yes vs no) as a prespecified subgroup, and the results say outcomes were generally consistent across subgroups (appendix figure S3, p. 9). The passages in our copy do not give the non-viral overall-survival HR of 0.86 or its 0.66–1.13 confidence interval, so the specific figures cannot be verified. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn LEAP-002, OS HR for viral HCC was 0.84 (0.67-1.05).
“In LEAP-002, outcomes for patients with viral and non-viral HCCs were similar, with HRs for OS being 0.84 (0.67–1.05) and 0.86 (0.66–1.13), respectively [36].”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [36]
The Statistical Analysis section (page unavailable) identifies viral aetiology as a prespecified subgroup, and the results say outcomes were generally consistent across subgroups. Our copy reports an overall-survival HR of 0.84 for all patients, but does not give the claimed 0.84 (0.67–1.05) specifically for patients with viral HCC; it refers subgroup results to appendix figure S3 (p. 9). (LLM, conf=0.77)
Experimental — accuracy not yet measuredMost previous phase 3 trials compared PD-1-based or PD-L1-based regimens with sorafenib, except the LEAP-002 trial, in which pembrolizumab plus lenvatinib did not show an overall survival benefit over lenvatinib plus placebo.
“By contrast, most of the previous phase 3 trials compared PD-1-based or PD-L1-based regimens with sorafenib, with the exception of the LEAP-002 trial, in which pembrolizumab plus lenvatinib did not show an overall survival benefit over lenvatinib plus placebo.22”
LEAP-002 reported 31.6% of patients having alcohol-related HCC.
“which reported 22.4% and 31.6% of patients having alcohol-related HCC, respectively”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [36]
The Results section says baseline disease characteristics are in table 1, but the table’s alcohol-related HCC figures are not present in our copy. Searches for alcohol-related aetiology and 31.6% found no passage reporting that proportion, so the claim cannot be checked against the available text. (LLM, conf=0.74)
Experimental — accuracy not yet measured
COSMIC-312 reported 22.4% of patients having alcohol-related HCC.
“which reported 22.4% and 31.6% of patients having alcohol-related HCC, respectively”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [36]
The References section identifies COSMIC-312 as a separate trial, but does not give its patients’ HCC aetiologies. Searches of the cited LEAP-002 paper for COSMIC-312, alcohol-related HCC, and 22.4% found no passage reporting the claimed figure. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe incidence of MASH-HCCs was only known in COSMIC-312.
“while the incidence of MASH-HCCs was only known in the former [35, 36]”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [36]
The LEAP-002 Statistical Analysis section lists viral-aetiology subgroups but does not report the incidence of MASH-associated HCC. Searches for MASH, NASH, steatohepatitis, and COSMIC-312 found no passage establishing that this incidence was known only in COSMIC-312; the References section merely lists that trial. Page numbers were not available in our copy. (LLM, conf=0.70)
Experimental — accuracy not yet measuredPatients with non-viral HCCs constituted 30-40% of the entire trial population.
“patients with non-viral HCCs only constituted 30–40% of the entire trial population”
From Etiology-Based Treatment for Unresectable/Advanced Hepatocellular Carcinoma: Focus on Viral Hepatitis and Metabolic Dysfunction-Associated Steatohepatitis (2025) · cites this paper as [36]
The Results report 794 randomized patients and refer to baseline characteristics in table 1, but the passages available from our copy do not give the number with non-viral HCC. The Statistical Analysis section mentions viral aetiology as a subgroup without reporting its prevalence. Searches for non-viral aetiology and the claimed 30–40% yielded no confirming figures. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Sorafenib in advanced hepatocellular carcinoma
Llovet, J. M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.-F., de Oliveira, A. C., Santoro, A., Raoul, J.-L., Forner, A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0708857 · Cited by 13,097 · see citing works
Self-citationToxicity and response criteria of the Eastern Cooperative Oncology Group
Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., Mcfadden, E. T., & Carbone, P. P. (1982) · American Journal of Clinical Oncology · doi:10.1097/00000421-198212000-00014 · Cited by 11,607 · see citing works
Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma
Finn, R. S., Qin, S., Ikeda, M., Galle, P. R., Ducreux, M., Kim, T.-Y., Kudo, M., Breder, V., Merle, P., Kaseb, A. O., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1915745 · Cited by 7,470 · see citing works
Self-citationLlovet, J. M., Kelley, R. K., Villanueva, A., Singal, A. G., Pikarsky, E., Roayaie, S., Lencioni, R., Koike, K., Zucman-Rossi, J., & Finn, R. S. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-00240-3 · Cited by 7,055 · see citing works
Self-citationKudo, M., Finn, R. S., Qin, S., Han, K.-H., Ikeda, K., Piscaglia, F., Baron, A., Park, J.-W., Han, G., Jassem, J., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30207-1 · Cited by 5,497 · see citing works
Self-citationVillanueva, A. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1713263 · Cited by 4,508 · see citing works
Modified RECIST (mRECIST) Assessment for Hepatocellular Carcinoma
Lencioni, R. A., & Llovet, J. M. (2010) · Seminars in Liver Disease · doi:10.1055/s-0030-1247132 · Cited by 4,354 · see citing works
Self-citationZhu, A. X., Finn, R. S., Edeline, J., Cattan, S., Ogasawara, S., Palmer, D., Verslype, C., Zagonel, V., Fartoux, L., Vogel, A., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30351-6 · Cited by 2,479 · see citing works
Self-citationAASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma
Singal, A. G., Llovet, J. M., Yarchoan, M., Mehta, N., Heimbach, J. K., Dawson, L. A., Jou, J. H., Kulik, L. M., Agopian, V. G., Marrero, J. A., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000466 · Cited by 2,052 · see citing works
Self-citationImmunotherapies for hepatocellular carcinoma
Llovet, J. M., Castet, F., Heikenwalder, M., Maini, M. K., Mazzaferro, V., Pinato, D. J., Pikarsky, E., Zhu, A. X., & Finn, R. S. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00573-2 · Cited by 1,843 · see citing works
Self-citationLenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma
Motzer, R. J., Alekseev, B. Y., Rha, S. Y., Porta, C., Eto, M., Powles, T. B., Grünwald, V., Hutson, T. E., Kopyltsov, E., Méndez-Vidal, M. J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2035716 · Cited by 1,804 · see citing works
Self-citationFinn, R. S., Ryoo, B.-Y., Merle, P., Kudo, M., Bouattour, M., Lim, H. Y., Breder, V., Edeline, J., Chao, Y., Ogasawara, S., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.01307 · Cited by 1,789 · see citing works
Self-citationTremelimumab plus durvalumab in unresectable hepatocellular carcinoma
Abou-Alfa, G. K., Lau, G., Kudo, M., Chan, S. L., Kelley, R. K., Furuse, J., Sukeepaisarnjaroen, W., Kang, Y.-K., Van Dao, T., De Toni, E. N., et al. (2022) · NEJM Evidence · doi:10.1056/evidoa2100070 · Cited by 1,576 · see citing works
Self-citationFinn, R. S., Ikeda, M., Zhu, A. X., Sung, M. W., Baron, A. D., Kudo, M., Okusaka, T., Kobayashi, M., Kumada, H., Kaneko, S., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.00808 · Cited by 1,167 · see citing works
Self-citationRen, Z., Xu, J., Bai, Y., Xu, A., Cang, S., Du, C., Li, Q., Lu, Y., Chen, Y., Guo, Y., et al. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00252-7 · Cited by 1,124 · see citing works
Self-citationComparative analysis of two rates
Miettinen, O. S., & Nurminen, M. M. (1985) · Statistics in Medicine · doi:10.1002/sim.4780040211 · Cited by 1,111 · see citing works
Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer
Makker, V., Colombo, N., Herráez, A. C., Santin, A. D., Colomba, E., Miller, D. S., Fujiwara, K., Pignata, S., Baron-Hay, S., Ray-Coquard, I. L., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2108330 · Cited by 965 · see citing works
Qin, S., Chan, S. L., Gu, S., Bai, Y., Ren, Z., Lin, X., Chen, Z., Jia, W., Jin, Y., Guo, Y., et al. (2023) · The Lancet · doi:10.1016/s0140-6736(23)00961-3 · Cited by 746 · see citing works
Self-citationKelley, R. K., Rimassa, L., Cheng, A.-L., Kaseb, A., Qin, S., Zhu, A. X., Chan, S. L., Melkadze, T., Sukeepaisarnjaroen, W., Breder, V., et al. (2022) · The Lancet Oncology · doi:10.1016/s1470-2045(22)00326-6 · Cited by 535 · see citing works
Self-citationQin, S., Bai, Y., Lim, H. Y., Thongprasert, S., Chao, Y., Fan, J., Yang, T., Bhudhisawasdi, V., Kang, W. K., Zhou, Y., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.5643 · Cited by 501 · see citing works
Self-citationA graphical approach to sequentially rejective multiple test procedures
Bretz, F., Maurer, W., Brannath, W., & Posch, M. (2009) · Statistics in Medicine · doi:10.1002/sim.3495 · Cited by 420 · see citing works
Qin, S., Bi, F., Gu, S., Bai, Y., Chen, Z., Wang, Z., Ying, J., Lu, Y., Meng, Z., Pan, H., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.21.00163 · Cited by 412 · see citing works
Self-citationSystemic treatment of hepatocellular carcinoma: An EASL position paper
Bruix, J., Chan, S. L., Galle, P. R., Rimassa, L., & Sangro, B. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.07.004 · Cited by 382 · see citing works
Self-citationTorrens, L., Montironi, C., Puigvehí, M., Mesropian, A., Leslie, J., Haber, P. K., Maeda, M., Balaseviciute, U., Willoughby, C. E., Abril‐Fornaguera, J., et al. (2021) · Hepatology · doi:10.1002/hep.32023 · Cited by 161 · see citing works
Self-citationQin, S., Finn, R. S., Kudo, M., Meyer, T., Vogel, A., Ducreux, M. P., Macarulla, T. M., Tomasello, G., Boisserie, F., Hou, J. W.-S., et al. (2019) · Future Oncology · doi:10.2217/fon-2019-0097 · Cited by 148 · see citing works
Self-citationQin, S., Chen, Z., Fang, W. J., Ren, Z., Xu, R., Ryoo, B., Meng, Z., Bai, Y., Chen, X., Liu, X., et al. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.2022.40.4_suppl.383 · Cited by 108 · see citing works
Self-citationVerset, G., Borbath, I., Karwal, M., Verslype, C., Vlierberghe, H. V., Kardosh, A., Zagonel, V., Stal, P. I., Sarker, D., Palmer, D. H., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-3807 · Cited by 92 · see citing works
Self-citationKim, C., Yang, H., Kim, I. H., Kang, B., Kim, H., Kim, H., Lee, W. S., Jung, S., Lim, H. Y., Cheon, J., et al. (2022) · JAMA Oncology · doi:10.1001/jamaoncol.2022.4733 · Cited by 59 · see citing works
Self-citationLlovet, J. M., Kudo, M., Merle, P., et al. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.2023.41.4_suppl.506 · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Yau, T., Galle, P. R., Decaens, T., Sangro, B., Qin, S., da Fonseca, L. G., Karachiwala, H., Blanc, J.-F., Park, J.-W., Gane, E., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)00403-9 · Cited by 390 · see citing works
Self-citationKudo, M., Ren, Z., Guo, Y., Han, G., Lin, H., Zheng, J., Ogasawara, S., Kim, J. H., Zhao, H., Li, C., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(24)02575-3 · Cited by 342 · see citing works
Self-citationSun, F. S. K., Wong, J. S. L., Mak, L.-Y., Wong, C. C.-L., Chew, V., Li, B. C. W., Leung, R., Cheung, T. T., & Yau, T. (2025) · Liver Cancer · doi:10.1159/000548536 · Cited by 2 · see citing works
- Authors
- Llovet, J. M., Kudo, M., Merle, P., Meyer, T., Qin, S., Ikeda, M., Xu, R., Edeline, J., Ryoo, B.-Y., Ren, Z., Masi, G., Kwiatkowski, M., Lim, H. Y., Kim, J. H., Breder, V., Kumada, H., Cheng, A.-L., Galle, P. R., Kaneko, S., Wang, A., Mody, K., Dutcus, C., Dubrovsky, L., Siegel, A. B., Finn, R. S., Strasser, S., Thompson, A., Roohullah, A., Sievert, W., Andelkovic, V., Knox, J., Davies, J., Asselah, J., Brahmania, M., Majeed, H., Villanueva, L., Yanez Weber, P., Garrido, M., Pizarro, G. I., Yanez, N., Xu, R., Ou, S., Ren, Z., Pan, H., Meng, Z., Gu, K., Chen, X., Zhang, T., Hao, C., Cao, P., Guo, Y., Qin, S., Xiao, J., Fang, W., Wang, X., Bai, Y., Chen, X., Yan, D., Zhao, H., Ying, J., Bonilla, C., Urrego, O., Zambrano, A., Lema, M., Restrepo Gutierrez, J. C., Cardona, A., Franco Millan, S., Oscar, M., Ramos, V., Merle, P., LeSourd, S., Edeline, J., Bronowicki, J.-P., Bourliere, M., Cattan, S., Bouattour, M., Mineur, L., Regnault, H., Dauvois, B., Schulze, K., Folprecht, G., Geier, A., Waidmann, O., Finkelmeier, F., Venerito, M., Berres, M.-L., Berg, T., Lange, C., Schmidt, H., Waldschmidt, D. T., Bitzer, M., McDermott, R., Duffy, A., Masi, G., Zagonel, V., Tonini, G., Piscaglia, F., Gori, S., Rizzo, M., Biscaldi, E., Foltran, L., Cabibbo, G., Ikeda, M., Kudo, M., Aikata, H., Numata, K., Marusawa, H., Kato, N., Kurosaki, M., Morimoto, M., Yamashita, T., Koga, H., Masaki, T., Tateishi, R., Inaba, Y., Arakawa, T., Suzuki, Y., Akua, N., Kobayashi, M., Hosaka, T., Nakamuta, M., Oza, N., Kondo, S., Furuse, J., Nagashima, F., Kitano, M., Takaguchi, K., Ryoo, B.-Y., Lim, H. Y., Kim, J. H., Kim, T.-Y., Kim, H. S., Hernandez Hernandez, C., Motola Kuba, D., Segura Gonzalez, M., Cabrera Luviano, J., Huitzil Melendez, F., Ramirez Godinez, F., Silva-Bravo, F., Gane, E., Stedman, C., Kwiatkowski, M., Wyrwicz, L., Nowakowska-Zajdel, E., Kraj, L., Janczewska, E., Surma-Wlodarczyk, R., Breder, V., Sekacheva, M., Orlova, R., Vasilyev, A., Zukov, R., Vladimirov, V., Minguez, B., Matilla Pena, A., Fernandez Castroagudin, J., Romero Gomez, M., Luis Lledo, J., Rubin, A., Garcia Sanchez, A., Calleja Panero, J., Yu, M.-C., Shen, Y.-C., Huang, Y.-H., Jeng, L.-B., Chang, T.-T., Yang, S.-S., Chen, S.-C., Dechaphunkul, A., Tanwandee, T., Leerapun, A., Seker, M., Harputluoglu, H., Cicin, I., Oksuzoglu, B., Bilici, M., Sezgin Goksu, S., Artac, M., Cil, T., Yalcin, S., Meyer, T., Sarker, D., Rao, A., Palmer, D., Evans, J., Hubner, R., Finn, R., Ulahannan, S., Zakari, A., Feun, L., Al-Rajabi, R., Sung, M., He, A., Kardosh, A., Goyal, L., Li, D., Goyal, L., Choi, M., Posada, J., Dodlapati, J., Shroff, R., Agrawal, S., Gopaluni, S., Akce, M., Alese, O., Baron, A., Dunne, R., Loaiza-Bonilla, A., & Frenette, C.
- Affiliations
- Hospital Clínic de Barcelona (ES)
- Toranomon Hospital (JP)
- National Taiwan University Hospital (TW)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Kanazawa University (JP)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Eisai (United States) (US)
- Seoul National University (KR)
- University of California, Los Angeles (US)
- Corresponding author
- Llovet, Josep M
- ORCID
- Llovet, Josep M
- Cheng, Ann-Lii
- Galle, Peter R
- Kaneko, Shuichi
- Wang, Anran
- Dutcus, Corina
- Dubrovsky, Leonid
- Siegel, Abby B
- Strasser, Simone
- Roohullah, Aflah
- Sievert, William
- Andelkovic, Vladimir
- Knox, Jennifer
- Davies, Janine
- Asselah, Jamil
- Brahmania, Mayur
- Pizarro, Gonzalo Ignacio
- Pan, Hongming
- Meng, Zhiqiang
- Gu, Kangsheng
- Chen, Xi
- Zhang, Tao
- Hao, Chunyi
- Cao, Peiguo
- Fang, Weijia
- Wang, Xin
- Bai, Yuxian
- Zhao, Hong
- Ying, Jieer
- Bonilla, Carlos
- Zambrano, Angela
- Lema, Mauricio
- Bronowicki, Jean-Pierre
- Bouattour, Mohamed
- Mineur, Laurent
- Schulze, Kornelius
- Folprecht, Gunnar
- Geier, Andreas
- Waidmann, Oliver
- Finkelmeier, Fabian
- Venerito, Marino
- Berres, Marie-Luise
- Berg, Thomas
- Lange, Christian
- Schmidt, Hartmut
- Bitzer, Michael
- McDermott, Ray
- Duffy, Austin
- Zagonel, Vittorina
- Tonini, Giuseppe
- Piscaglia, Fabio
- Gori, Stefania
- Rizzo, Mimma
- Biscaldi, Elisa
- Foltran, Luisa
- Cabibbo, Giuseppe
- Aikata, Hiroshi
- Numata, Kazushi
- Marusawa, Hiroyuki
- Kato, Naoya
- Kurosaki, Masayuki
- Morimoto, Manabu
- Yamashita, Tatsuya
- Koga, Hironori
- Masaki, Tsutomu
- Tateishi, Ryosuke
- Inaba, Yoshitaka
- Suzuki, Yoshiyuki
- Kobayashi, Masahiro
- Hosaka, Tetsuya
- Nakamuta, Makoto
- Oza, Noriko
- Kondo, Shunsuke
- Furuse, Junji
- Nagashima, Fumio
- Kitano, Masayuki
- Takaguchi, Koichi
- Kim, Han Sang
- Silva-Bravo, Fernando
- Gane, Edward
- Stedman, Catherine
- Wyrwicz, Lucjan
- Kraj, Leszek
- Janczewska, Ewa
- Sekacheva, Marina
- Zukov, Ruslan
- Yu, Ming-Chin
- Shen, Ying-Chun
- Huang, Yi-Hsiang
- Jeng, Long-Bin
- Yang, Sheng-Shun
- Chen, Shinn-Cherng
- Dechaphunkul, Arunee
- Tanwandee, Tawesak
- Leerapun, Apinya
- Bilici, Mehmet
- Sarker, Debashis
- Rao, Ankit
- Palmer, Daniel
- Hubner, Richard
- Ulahannan, Susanna
- Feun, Lynn
- Al-Rajabi, Raed
- Sung, Max
- He, Aiwu
- Kardosh, Adel
- Li, Daneng
- Shroff, Rachna
- Agrawal, Saurabh
- Akce, Mehmet
- Alese, Olatunji
- Baron, Ari
- Frenette, Catherine
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2023-12
- Volume
- 24
- Issue
- 12
- Pages
- 1399-1410
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W4389074118
- Cited by
- 469
- References
- 29
- Citations by year
- 2026: 135 · 2025: 191 · 2024: 139 · 2023: 3
- FWCI
- 79.12
- Type
- journal article
- Language
- en
- Update notices
- erratum (2024-04-01)
- Open access
- green
- discovery.ucl.ac.uk
- Licence
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by-nc-nd)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- Eisai
- Meso Scale Diagnostics
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Keywords
- lenvatinib, pembrolizumab, hepatocellular carcinoma, first-line therapy, immune checkpoint inhibitors, tyrosine kinase inhibitors, combination therapy, overall survival, progression-free survival, alpha-fetoprotein, portal vein invasion, extrahepatic spread
- MeSH terms
- Aged, Antineoplastic Combined Chemotherapy Protocols, Double-Blind Method, Female, Gastrointestinal Hemorrhage, Carcinoma, Hepatocellular, Hepatorenal Syndrome, Humans, Liver Neoplasms, Male, Middle Aged, Phenylurea Compounds, Quinolines, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
