Journal Article
. 2020 Jul; 38(26):2960-2970.
doi: 10.1200/JCO.20.00808.

Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma

Richard S Finn 1 Masafumi Ikeda 2 Andrew X Zhu 3 Max W Sung 4 Ari D Baron 5 Masatoshi Kudo 6 Takuji Okusaka 7 Masahiro Kobayashi 8 Hiromitsu Kumada 8 Shuichi Kaneko 9 Marc Pracht 10 Konstantin Mamontov 11 Tim Meyer 12 Tomoki Kubota 13 Corina E Dutcus 14 Kenichi Saito 14 Abby B Siegel 15 Leonid Dubrovsky 15 Kalgi Mody 14 Josep M Llovet 16 
Affiliations
  • PMID: 32716739
  •     25 References
  •     185 citations

Abstract

Purpose: The immunomodulatory effect of lenvatinib (a multikinase inhibitor) on tumor microenvironments may contribute to antitumor activity when combined with programmed death receptor-1 (PD-1) signaling inhibitors in hepatocellular carcinoma (HCC). We report results from a phase Ib study of lenvatinib plus pembrolizumab (an anti-PD-1 antibody) in unresectable HCC (uHCC).

Patients And Methods: In this open-label multicenter study, patients with uHCC received lenvatinib (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily and pembrolizumab 200 mg intravenously on day 1 of a 21-day cycle. The study included a dose-limiting toxicity (DLT) phase and an expansion phase (first-line patients). Primary objectives were safety/tolerability (DLT phase), and objective response rate (ORR) and duration of response (DOR) by modified RECIST (mRECIST) and RECIST version 1.1 (v1.1) per independent imaging review (IIR; expansion phase).

Results: A total of 104 patients were enrolled. No DLTs were reported (n = 6) in the DLT phase; 100 patients (expansion phase; included n = 2 from DLT phase) had received no prior systemic therapy and had Barcelona Clinic Liver Cancer stage B (n = 29) or C disease (n = 71). At data cutoff, 37% of patients remained on treatment. Median duration of follow-up was 10.6 months (95% CI, 9.2 to 11.5 months). Confirmed ORRs by IIR were 46.0% (95% CI, 36.0% to 56.3%) per mRECIST and 36.0% (95% CI, 26.6% to 46.2%) per RECIST v1.1. Median DORs by IIR were 8.6 months (95% CI, 6.9 months to not estimable [NE]) per mRECIST and 12.6 months (95% CI, 6.9 months to NE) per RECIST v1.1. Median progression-free survival by IIR was 9.3 months per mRECIST and 8.6 months per RECIST v1.1. Median overall survival was 22 months. Grade ≥ 3 treatment-related adverse events occurred in 67% (grade 5, 3%) of patients. No new safety signals were identified.

Conclusion: Lenvatinib plus pembrolizumab has promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.

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Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome.
Sally Temraz, Farah Nassar, +3 authors, Rihab Nasr.
Int J Mol Sci, 2021 Aug 08; 22(15). PMID: 34360566    Free PMC article.
Review.
[Research Progress of Adverse Events Related to PD-1/PD-L1 Inhibitors 
Based Combination Therapy].
Xiaoyu Guo, Ti Wen, Xiujuan Qu.
Zhongguo Fei Ai Za Zhi, 2021 Jul 20; 24(7). PMID: 34275517    Free PMC article.
Review.
Advances of Targeted Therapy for Hepatocellular Carcinoma.
Mengke Niu, Ming Yi, +2 authors, Kongming Wu.
Front Oncol, 2021 Aug 13; 11. PMID: 34381735    Free PMC article.
Review.
PD-1 Blockade for Hepatocellular Carcinoma: Current Research and Future Prospects.
Antonio D'Alessio, Lorenza Rimassa, Alessio Cortellini, David James Pinato.
J Hepatocell Carcinoma, 2021 Aug 14; 8. PMID: 34386437    Free PMC article.
Review.
Immune suppressive checkpoint interactions in the tumour microenvironment of primary liver cancers.
Guoying Zhou, Patrick P C Boor, +2 authors, Jaap Kwekkeboom.
Br J Cancer, 2021 Aug 18; 126(1). PMID: 34400801    Free PMC article.
Review.
Combination of Sorafenib, Camrelizumab, Transcatheter Arterial Chemoembolization, and Stereotactic Body Radiation Therapy as a Novel Downstaging Strategy in Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Case Series Study.
Yun Huang, Zeyu Zhang, +2 authors, Zhiming Wang.
Front Oncol, 2021 Aug 20; 11. PMID: 34408974    Free PMC article.
Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations.
Xiao-Dong Zhu, Cheng Huang, +12 authors, Hui-Chuan Sun.
Liver Cancer, 2021 Aug 21; 10(4). PMID: 34414120    Free PMC article.
Emerging treatment modalities for systemic therapy in hepatocellular carcinoma.
Xin Qing, Wenjing Xu, +3 authors, Yewei Zhang.
Biomark Res, 2021 Aug 23; 9(1). PMID: 34419152    Free PMC article.
Review.
Downstaging and resection of hepatocellular carcinoma in patients with extrahepatic metastases after stereotactic therapy.
Xiaobo Yang, Haifeng Xu, +13 authors, Haitao Zhao.
Hepatobiliary Surg Nutr, 2021 Aug 26; 10(4). PMID: 34430522    Free PMC article.
Lenvatinib plus TACE with or without pembrolizumab for the treatment of initially unresectable hepatocellular carcinoma harbouring PD-L1 expression: a retrospective study.
Song Chen, Zhiqiang Wu, +9 authors, Wenbo Guo.
J Cancer Res Clin Oncol, 2021 Aug 29;. PMID: 34453221
NAFLD-Related Hepatocarcinoma: The Malignant Side of Metabolic Syndrome.
Anna Michelotti, Marco de Scordilli, +6 authors, Fabio Puglisi.
Cells, 2021 Aug 28; 10(8). PMID: 34440803    Free PMC article.
Review.
Natural Killer Cells and Type 1 Innate Lymphoid Cells in Hepatocellular Carcinoma: Current Knowledge and Future Perspectives.
Nicolas Jacquelot, Cyril Seillet, +3 authors, Pamela S Ohashi.
Int J Mol Sci, 2021 Aug 28; 22(16). PMID: 34445750    Free PMC article.
Review.
Tyrosine Kinase Inhibitors Stimulate HLA Class I Expression by Augmenting the IFNγ/STAT1 Signaling in Hepatocellular Carcinoma Cells.
Aya Takahashi, Atsushi Umemura, +8 authors, Yoshito Itoh.
Front Oncol, 2021 Aug 31; 11. PMID: 34458148    Free PMC article.
Identification of Regorafenib Prognostic Index (REP Index) via Recursive Partitioning Analysis in Patients with Advanced Hepatocellular Carcinoma Receiving Systemic Treatment: A Real-World Multi-Institutional Experience.
Margherita Rimini, Changhoon Yoo, +15 authors, Andrea Casadei-Gardini.
Target Oncol, 2021 Sep 08; 16(5). PMID: 34491510
Immunotherapy in Hepatocellular Carcinoma.
Claudia A M Fulgenzi, Thomas Talbot, +4 authors, David J Pinato.
Curr Treat Options Oncol, 2021 Aug 24; 22(10). PMID: 34424422    Free PMC article.
Review.
Case Report: Complete Response of Primary Massive Hepatocellular Carcinoma to Anti-Programmed Death Ligand-1 Antibody Following Progression on Anti-Programmed Death-1 Antibody.
Gang Liu, Wenxuan Zhou, +4 authors, Liansheng Gong.
Front Immunol, 2021 Sep 11; 12. PMID: 34504494    Free PMC article.
Application of Immunotherapy in Hepatocellular Carcinoma.
Lele Miao, Zhengchao Zhang, Zhijian Ren, Yumin Li.
Front Oncol, 2021 Sep 14; 11. PMID: 34513678    Free PMC article.
Review.
Deep Learning-Based Prediction of Future Extrahepatic Metastasis and Macrovascular Invasion in Hepatocellular Carcinoma.
Sirui Fu, Meiqing Pan, +14 authors, Jie Tian.
J Hepatocell Carcinoma, 2021 Sep 14; 8. PMID: 34513748    Free PMC article.
Improving antitumor immunity using antiangiogenic agents: Mechanistic insights, current progress, and clinical challenges.
Shu-Jin Li, Jia-Xian Chen, Zhi-Jun Sun.
Cancer Commun (Lond), 2021 Jun 18; 41(9). PMID: 34137513    Free PMC article.
Review.
Systemic Sequential Therapy of CisGem, Tislelizumab, and Lenvatinib for Advanced Intrahepatic Cholangiocarcinoma Conversion Therapy.
Yuan Ding, Xin Han, +3 authors, Weilin Wang.
Front Oncol, 2021 Sep 17; 11. PMID: 34527576    Free PMC article.
Review.
Efficacy and Safety of Anti-Programmed Cell Death Protein-1 Immunotherapy for Advanced Hepatocellular Carcinoma With Pulmonary Metastases: A Single-Center, Retrospective Study.
Mei Zhao, Yiruo Zhang, +3 authors, Yingying Du.
Technol Cancer Res Treat, 2021 Sep 17; 20. PMID: 34525851    Free PMC article.
Efficacy and safety of lenvatinib monotreatment and lenvatinib-based combination therapy for patients with unresectable hepatocellular carcinoma: a retrospective, real-world study in China.
Yun Zhu, Penghui Sun, +7 authors, Yang Cheng.
Cancer Cell Int, 2021 Sep 20; 21(1). PMID: 34537075    Free PMC article.
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma.
Tim F Greten, Ghassan K Abou-Alfa, +18 authors, Ignacio Melero.
J Immunother Cancer, 2021 Sep 15; 9(9). PMID: 34518290    Free PMC article.
Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma.
Xinhe Zhang, Lin Guan, +7 authors, Yiling Li.
Front Oncol, 2021 Sep 28; 11. PMID: 34568017    Free PMC article.
Review.
Multi-Omics Analysis of the Anti-tumor Synergistic Mechanism and Potential Application of Immune Checkpoint Blockade Combined With Lenvatinib.
Yuting Lu, Jiangtao Jin, +5 authors, Qin Li.
Front Cell Dev Biol, 2021 Sep 28; 9. PMID: 34568339    Free PMC article.
Spontaneous Immune-Mediated Regression of Hepatocellular Carcinoma With High Tumor Mutational Burden.
Joseph W Franses, Irun Bhan, +3 authors, Kenneth Tanabe.
JCO Precis Oncol, 2021 Sep 30; 5. PMID: 34585041    Free PMC article.
How Immunotherapy Has Changed the Continuum of Care in Hepatocellular Carcinoma.
Giulia Martini, Davide Ciardiello, +12 authors, Erika Martinelli.
Cancers (Basel), 2021 Sep 29; 13(18). PMID: 34572944    Free PMC article.
Review.
Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy.
Ji-Won Han, Seung-Kew Yoon.
Pharmaceutics, 2021 Sep 29; 13(9). PMID: 34575463    Free PMC article.
Review.
Immune aspects of hepatocellular carcinoma: From immune markers for early detection to immunotherapy.
Ângelo Z Mattos, Jose D Debes, +2 authors, Angelo A Mattos.
World J Gastrointest Oncol, 2021 Oct 08; 13(9). PMID: 34616518    Free PMC article.
Review.
Multimodal Strategy in Localized Merkel Cell Carcinoma: Where Are We and Where Are We Heading?
Gianluca Ricco, Elisa Andrini, +6 authors, Giuseppe Lamberti.
Int J Mol Sci, 2021 Oct 14; 22(19). PMID: 34638968    Free PMC article.
Review.
Viral Status and Efficacy of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis.
Ziniu Ding, Zhaoru Dong, +8 authors, Tao Li.
Front Immunol, 2021 Oct 19; 12. PMID: 34659220    Free PMC article.
Systematic Review.
Donafenib in Chinese patients with advanced hepatocellular carcinoma (HCC): Really a new standard of care, or should we change paradigm for drug development in HCC?
Francesca Negri, Camillo Porta.
Oncol Rev, 2021 Oct 21; 15(2). PMID: 34667489    Free PMC article.
Early Prediction of Objective Response of Fibrinogen in a Real-World Cohort of Hepatocellular Carcinoma Cases Treated by Programmed Cell Death Receptor-1 and Lenvatinib.
Yanjun Shen, Huige Wang, Jianying Wei, Wendong Li.
Onco Targets Ther, 2021 Oct 23; 14. PMID: 34675546    Free PMC article.
Immunotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects.
Zhuoyan Liu, Xuan Liu, +5 authors, Xiaotao Jiang.
Front Immunol, 2021 Oct 23; 12. PMID: 34675942    Free PMC article.
Review.
Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study.
Jia-Yi Wu, Zhen-Yu Yin, +8 authors, Mao-Lin Yan.
J Hepatocell Carcinoma, 2021 Oct 23; 8. PMID: 34676181    Free PMC article.
HCC and Molecular Targeting Therapies: Back to the Future.
Luca Rinaldi, Erica Vetrano, +4 authors, Ferdinando Carlo Sasso.
Biomedicines, 2021 Oct 24; 9(10). PMID: 34680462    Free PMC article.
Review.
Pembrolizumab plus lenvatinib with or without hepatic arterial infusion chemotherapy in selected populations of patients with treatment-naive unresectable hepatocellular carcinoma exhibiting PD-L1 staining: a multicenter retrospective study.
Song Chen, Bo Xu, +7 authors, Wenbo Guo.
BMC Cancer, 2021 Oct 22; 21(1). PMID: 34670506    Free PMC article.
Advanced hepatocellular carcinoma with response to lenvatinib after atezolizumab plus bevacizumab.
Shigeki Yano, Tomokazu Kawaoka, +24 authors, Hiroshi Aikata.
Medicine (Baltimore), 2021 Oct 23; 100(42). PMID: 34678902    Free PMC article.
Mesoporous Silica Nanoparticles for Potential Immunotherapy of Hepatocellular Carcinoma.
Han Wu, Xin-Fei Xu, +8 authors, Tian Yang.
Front Bioeng Biotechnol, 2021 Oct 26; 9. PMID: 34692650    Free PMC article.
Review.
Improving Outcomes of Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma: New Data and Ongoing Trials.
Lisha Mou, Xiaohe Tian, +13 authors, Zuhui Pu.
Front Oncol, 2021 Oct 29; 11. PMID: 34707994    Free PMC article.
Review.
Baseline Liver Function and Subsequent Outcomes in the Phase 3 REFLECT Study of Patients with Unresectable Hepatocellular Carcinoma.
Arndt Vogel, Catherine Frenette, +10 authors, Masatoshi Kudo.
Liver Cancer, 2021 Nov 02; 10(5). PMID: 34721512    Free PMC article.
Camrelizumab Plus Sorafenib Versus Sorafenib Monotherapy for Advanced Hepatocellular Carcinoma: A Retrospective Analysis.
Qinqin Liu, Nan You, +6 authors, Lu Zheng.
Front Oncol, 2021 Nov 06; 11. PMID: 34737945    Free PMC article.
Surgery After Conversion Therapy With PD-1 Inhibitors Plus Tyrosine Kinase Inhibitors Are Effective and Safe for Advanced Hepatocellular Carcinoma: A Pilot Study of Ten Patients.
Wenwen Zhang, Bingyang Hu, +14 authors, Shichun Lu.
Front Oncol, 2021 Nov 06; 11. PMID: 34737958    Free PMC article.
Response Stratification in the First-Line Combined Immunotherapy of Hepatocellular Carcinoma at Genomic, Transcriptional and Immune Repertoire Levels.
Jiamin Cheng, Yinyin Li, +10 authors, Zhen Zeng.
J Hepatocell Carcinoma, 2021 Nov 06; 8. PMID: 34737983    Free PMC article.
Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Progresses and Challenges.
Hao-Tian Liu, Meng-Jie Jiang, +5 authors, Jian-Hong Zhong.
Front Oncol, 2021 Nov 09; 11. PMID: 34745958    Free PMC article.
Review.
Research progress regarding programmed cell death 1/programmed cell death ligand 1 inhibitors combined with targeted therapy for treating hepatocellular carcinoma.
Lin-Lin Zheng, Chang-Cheng Tao, +4 authors, Wei-Qi Rong.
World J Gastrointest Surg, 2021 Nov 11; 13(10). PMID: 34754383    Free PMC article.
Review.
The upward trend in the immunotherapy utilization for hepatobiliary cancers.
Xiao-Bu Lan, George Papatheodoridis, Yu-Xian Teng, Jian-Hong Zhong.
Hepatobiliary Surg Nutr, 2021 Nov 12; 10(5). PMID: 34760976    Free PMC article.
Immunotherapies for hepatocellular carcinoma.
Josep M Llovet, Florian Castet, +6 authors, Richard S Finn.
Nat Rev Clin Oncol, 2021 Nov 13; 19(3). PMID: 34764464
Review.
The past, present and future of conversion therapy for liver cancer.
Tianqiang Song, Mengran Lang, +2 authors, Wei Lu.
Am J Cancer Res, 2021 Nov 13; 11(10). PMID: 34765289    Free PMC article.
Review.
Atractylodin may induce ferroptosis of human hepatocellular carcinoma cells.
Yongfei He, Dalang Fang, +11 authors, Tao Peng.
Ann Transl Med, 2021 Nov 19; 9(20). PMID: 34790741    Free PMC article.
Advances in locoregional therapy for hepatocellular carcinoma combined with immunotherapy and targeted therapy.
Jian Xue, Hongbo Ni, +2 authors, Meng Niu.
J Interv Med, 2021 Nov 23; 4(3). PMID: 34805958    Free PMC article.
Review.
Safety Profile of Immunotherapy Combined With Antiangiogenic Therapy in Patients With Melanoma: Analysis of Three Clinical Studies.
Hui Tian, Xuan Wang, +12 authors, Jun Guo.
Front Pharmacol, 2021 Dec 04; 12. PMID: 34858178    Free PMC article.
Immunotherapy of HBV-related advanced hepatocellular carcinoma with short-term HBV-specific TCR expressed T cells: results of dose escalation, phase I trial.
Fanping Meng, Jinfang Zhao, +21 authors, Fu-Sheng Wang.
Hepatol Int, 2021 Dec 02; 15(6). PMID: 34850325    Free PMC article.
Surgical Conversion for Initially Unresectable Locally Advanced Hepatocellular Carcinoma Using a Triple Combination of Angiogenesis Inhibitors, Anti-PD-1 Antibodies, and Hepatic Arterial Infusion Chemotherapy: A Retrospective Study.
Jinliang Zhang, Xihao Zhang, +4 authors, Ti Zhang.
Front Oncol, 2021 Dec 07; 11. PMID: 34868921    Free PMC article.
Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study.
Xiaozhun Huang, Lin Xu, +6 authors, Xu Che.
Front Oncol, 2021 Dec 07; 11. PMID: 34868952    Free PMC article.
Downstaging Conversion Therapy in Patients With Initially Unresectable Advanced Hepatocellular Carcinoma: An Overview.
Hui-Chuan Sun, Xiao-Dong Zhu.
Front Oncol, 2021 Dec 07; 11. PMID: 34869008    Free PMC article.
Review.
PRRC2A Promotes Hepatocellular Carcinoma Progression and Associates with Immune Infiltration.
Xin Liu, Yize Zhang, +6 authors, Zujiang Yu.
J Hepatocell Carcinoma, 2021 Dec 10; 8. PMID: 34881207    Free PMC article.
Revisiting Hepatic Artery Infusion Chemotherapy in the Treatment of Advanced Hepatocellular Carcinoma.
Ching-Tso Chen, Tsung-Hao Liu, +3 authors, Zhong-Zhe Lin.
Int J Mol Sci, 2021 Dec 11; 22(23). PMID: 34884684    Free PMC article.
Review.
Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma.
Rui Xing, Jinping Gao, Qi Cui, Qian Wang.
Front Immunol, 2021 Dec 14; 12. PMID: 34899747    Free PMC article.
Review.
Lenvatinib Plus PD-1 Inhibitors as First-Line Treatment in Patients With Unresectable Biliary Tract Cancer: A Single-Arm, Open-Label, Phase II Study.
Qiyi Zhang, Xingyu Liu, +5 authors, Sheng Yan.
Front Oncol, 2021 Dec 14; 11. PMID: 34900698    Free PMC article.
Correlation Between Immune-Related Adverse Events and Prognosis in Hepatocellular Carcinoma Patients Treated With Immune Checkpoint Inhibitors.
Shuo Xu, Ruixue Lai, +3 authors, Zhanjun Guo.
Front Immunol, 2021 Dec 25; 12. PMID: 34950153    Free PMC article.
Combined Stereotactic Body Radiotherapy and Immunotherapy Versus Transarterial Chemoembolization in Locally Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.
Chi-Leung Chiang, Keith Wan-Hang Chiu, +2 authors, Albert Chi-Yan Chan.
Front Oncol, 2021 Dec 25; 11. PMID: 34950594    Free PMC article.
Is There Still a Place for Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma at the Time of Immunotherapies? A Focus on Lenvatinib.
Marie Decraecker, Caroline Toulouse, Jean-Frédéric Blanc.
Cancers (Basel), 2021 Dec 25; 13(24). PMID: 34944930    Free PMC article.
Review.
Immunotherapy for Hepatocellular Carcinoma: New Prospects for the Cancer Therapy.
Rossella Fasano, Mahdi Abdoli Shadbad, +6 authors, Nicola Silvestris.
Life (Basel), 2021 Dec 25; 11(12). PMID: 34947886    Free PMC article.
Review.
Response Evaluation and Survival Prediction Following PD-1 Inhibitor in Patients With Advanced Hepatocellular Carcinoma: Comparison of the RECIST 1.1, iRECIST, and mRECIST Criteria.
Meng Zhou, Chunhui Zhang, +8 authors, Tongsen Zheng.
Front Oncol, 2021 Dec 28; 11. PMID: 34956885    Free PMC article.
Immunotherapy in Gastrointestinal Malignancies.
Rishi Surana, Shubham Pant.
Adv Exp Med Biol, 2022 Jan 02; 1342. PMID: 34972968
A Retrospective Study of Lenvatinib Monotherapy or Combined With Programmed Cell Death Protein 1 Antibody in the Treatment of Patients With Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma in China.
Sihui Zhu, Chenxi Liu, +3 authors, Jie Shen.
Front Oncol, 2022 Jan 04; 11. PMID: 34976828    Free PMC article.
Complete Response to PD-1 Inhibitor in Primary Hepatocellular Carcinoma Patients Post-Progression on Bi-Specific Antibody Conjugated CIK Cell Treatment: A Report of Two Cases.
Tong Wu, Linzhi Zhang, +4 authors, Yinying Lu.
Onco Targets Ther, 2022 Jan 06; 14. PMID: 34984004    Free PMC article.
The Efficacy of TACE Combined With Lenvatinib Plus Sintilimab in Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study.
Fei Cao, Yi Yang, +6 authors, Jiaping Zheng.
Front Oncol, 2022 Jan 07; 11. PMID: 34988019    Free PMC article.
Recent advances in systemic therapy for hepatocellular carcinoma.
Huajun Zhang, Wuyang Zhang, Longying Jiang, Yongheng Chen.
Biomark Res, 2022 Jan 11; 10(1). PMID: 35000616    Free PMC article.
Review.
Systemic treatment of hepatocellular carcinoma: the times they are a-changin'.
Claudia Campani, Jean-Charles Nault.
Hepatobiliary Surg Nutr, 2022 Jan 11; 10(6). PMID: 35004965    Free PMC article.
Alpha-fetoprotein response predicts treatment outcomes in patients with unresectable hepatocellular carcinoma receiving immune checkpoint inhibitors with or without tyrosine kinase inhibitors or locoregional therapies.
Wei-Fan Hsu, Hung-Wei Wang, +14 authors, Cheng-Yuan Peng.
Am J Cancer Res, 2022 Jan 13; 11(12). PMID: 35018250    Free PMC article.
Intrahepatic cholangiocarcinoma: Morpho-molecular pathology, tumor reactive microenvironment, and malignant progression.
Alphonse E Sirica, Mario Strazzabosco, Massimiliano Cadamuro.
Adv Cancer Res, 2021 Feb 14; 149. PMID: 33579427    Free PMC article.
Review.
Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons.
Yi Luo, Fei Teng, Hong Fu, Guo-Shan Ding.
World J Gastrointest Oncol, 2022 Feb 05; 14(1). PMID: 35116109    Free PMC article.
Review.
Single-cell immune signature for detecting early-stage HCC and early assessing anti-PD-1 immunotherapy efficacy.
Jiawei Shi, Junwei Liu, +9 authors, Weijia Fang.
J Immunother Cancer, 2022 Feb 02; 10(1). PMID: 35101942    Free PMC article.
Overexpression of BACH1 mediated by IGF2 facilitates hepatocellular carcinoma growth and metastasis via IGF1R and PTK2.
Meng Xie, Mengyu Sun, +8 authors, Limin Xia.
Theranostics, 2022 Feb 15; 12(3). PMID: 35154476    Free PMC article.
Surufatinib plus toripalimab in patients with advanced solid tumors: a single-arm, open-label, phase 1 trial.
Yanshuo Cao, Ming Lu, +10 authors, Lin Shen.
J Cancer Res Clin Oncol, 2022 Feb 16;. PMID: 35166929
Immunotherapies for hepatocellular carcinoma.
Justin K H Liu, Andrew F Irvine, Rebecca L Jones, Adel Samson.
Cancer Med, 2021 Dec 26; 11(3). PMID: 34953051    Free PMC article.
Review.
Ferroptosis Regulator Modification Patterns and Tumor Microenvironment Immune Infiltration Characterization in Hepatocellular Carcinoma.
Dong-Li Liu, Ming-Yao Wu, Tie-Ning Zhang, Chun-Gang Wang.
Front Mol Biosci, 2022 Feb 15; 9. PMID: 35155577    Free PMC article.
Recent Advances in Systemic Therapies for Advanced Hepatocellular Carcinoma.
Gabriella Aitcheson, Anjana Pillai, Bassam Dahman, Binu V John.
Curr Hepatol Rep, 2021 Feb 09; 20(1). PMID: 33552839    Free PMC article.
Review.
Apatinib Plus Camrelizumab With/Without Chemoembolization for Hepatocellular Carcinoma: A Real-World Experience of a Single Center.
Shuguang Ju, Chen Zhou, +9 authors, Bin Xiong.
Front Oncol, 2022 Feb 18; 11. PMID: 35174073    Free PMC article.
Effectiveness of fourth-line dual immunotherapy in hepatocellular carcinoma with simultaneous steroid administration for immune-related hepatitis.
Kristina Lowes, Johanna Reinecke, +11 authors, Ute Koenig.
Therap Adv Gastroenterol, 2022 Feb 19; 15. PMID: 35178123    Free PMC article.
Identification and validation a costimulatory molecule gene signature to predict the prognosis and immunotherapy response for hepatocellular carcinoma.
Yinan Hu, Jingyi Liu, +7 authors, Ying Han.
Cancer Cell Int, 2022 Feb 24; 22(1). PMID: 35193632    Free PMC article.
Therapeutic Vaccines against Hepatocellular Carcinoma in the Immune Checkpoint Inhibitor Era: Time for Neoantigens?
David Repáraz, Belén Aparicio, +2 authors, Pablo Sarobe.
Int J Mol Sci, 2022 Feb 27; 23(4). PMID: 35216137    Free PMC article.
Review.
Clinical application of gelatin sponge microparticles-transcatheter arterial chemoembolization combined with synchronous antigen-presenting dendritic cell sequential reinfusion for treatment of advanced large liver cancer: A single-center, prospective, non-randomized, controlled trial.
Guang Sheng Zhao, Song Liu, +6 authors, Yue Wei Zhang.
Medicine (Baltimore), 2022 Feb 26; 101(8). PMID: 35212274    Free PMC article.
Treatments of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: Current Status and Controversy.
Zhu-Jian Deng, Le Li, +7 authors, Jian-Hong Zhong.
J Clin Transl Hepatol, 2022 Mar 03; 10(1). PMID: 35233384    Free PMC article.
Review.
Phase 1b trial of anti-VEGF/PDGFR vorolanib combined with immune checkpoint inhibitors in patients with advanced solid tumors.
Nusayba A Bagegni, Haeseong Park, +11 authors, Andrea Wang-Gillam.
Cancer Chemother Pharmacol, 2022 Mar 06; 89(4). PMID: 35247086    Free PMC article.
Glypican-3: A Novel and Promising Target for the Treatment of Hepatocellular Carcinoma.
Xiufeng Zheng, Xun Liu, +2 authors, Ming Liu.
Front Oncol, 2022 Mar 08; 12. PMID: 35251989    Free PMC article.
Review.
PD-1/PD-L1 Immuno-Mediated Therapy in NAFLD: Advantages and Obstacles in the Treatment of Advanced Disease.
Rosa Lombardi, Roberto Piciotti, +3 authors, Anna Ludovica Fracanzani.
Int J Mol Sci, 2022 Mar 11; 23(5). PMID: 35269846    Free PMC article.
Review.
Real-world Treatment Patterns and Reasons for Therapy Selection in Patients with Advanced Hepatocellular Carcinoma in US Oncology Practices.
Andrew J Klink, Landon Z Marshall, +3 authors, Bruce Feinberg.
Oncologist, 2022 Mar 12; 27(3). PMID: 35274709    Free PMC article.
A narrative review of systemic treatment options for hepatocellular carcinoma: state of the art review.
Joy Awosika, Davendra Sohal.
J Gastrointest Oncol, 2022 Mar 15; 13(1). PMID: 35284102    Free PMC article.
Review.
Lenvatinib Plus Camrelizumab vs. Lenvatinib Monotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study.
Qi Li, Mengran Cao, +9 authors, Jinzhang Chen.
Front Oncol, 2022 Mar 15; 12. PMID: 35280760    Free PMC article.
The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment.
Haoyue Hu, Yue Chen, +5 authors, Jun He.
Front Immunol, 2022 Mar 15; 13. PMID: 35281003    Free PMC article.
Review.
Transarterial Chemoembolization Combined With Lenvatinib Plus PD-1 Inhibitor for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study.
Mingyue Cai, Wensou Huang, +9 authors, Kangshun Zhu.
Front Immunol, 2022 Mar 19; 13. PMID: 35300325    Free PMC article.
Real-world efficiency of lenvatinib plus PD-1 blockades in advanced hepatocellular carcinoma: an exploration for expanded indications.
Xuqi Sun, Qi Zhang, +3 authors, Tingbo Liang.
BMC Cancer, 2022 Mar 21; 22(1). PMID: 35305593    Free PMC article.
A Retrospective Study on Therapeutic Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors Plus Lenvatinib in Patients With Unresectable Hepatocellular Carcinoma.
Ying Teng, Xiaoyan Ding, +2 authors, Jinglong Chen.
Technol Cancer Res Treat, 2022 Mar 23; 21. PMID: 35313780    Free PMC article.
Lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable hepatocellular carcinoma.
Chi-Jung Wu, Pei-Chang Lee, +5 authors, Yi-Hsiang Huang.
Cancer Immunol Immunother, 2022 Mar 30;. PMID: 35347395
The Treatment Landscape of Advanced Hepatocellular Carcinoma.
Kit Man Wong, Gentry G King, William P Harris.
Curr Oncol Rep, 2022 Mar 30; 24(7). PMID: 35347594
Review.
Immune Checkpoint Inhibitor-Based Systemic Therapy Shows Remarkable Curative Effect in a Hepatocellular Carcinoma Patient With Intractable Postoperative Recurrence and Metastases: A Case Report and Literature Review.
Xing He, Yaorong Peng, Zhenyu Zhou, Wenbin Li.
Front Oncol, 2022 Apr 05; 12. PMID: 35372050    Free PMC article.
Physical activity improves outcomes of combined lenvatinib plus anti-PD-1 therapy in unresectable hepatocellular carcinoma: a retrospective study and mouse model.
Xue-Feng Liu, Xiao-Dong Zhu, +7 authors, Zhao-You Tang.
Exp Hematol Oncol, 2022 Apr 06; 11(1). PMID: 35379324    Free PMC article.
Randomized Phase 3 LEAP-012 Study: Transarterial Chemoembolization With or Without Lenvatinib Plus Pembrolizumab for Intermediate-Stage Hepatocellular Carcinoma Not Amenable to Curative Treatment.
Josep M Llovet, Arndt Vogel, +8 authors, Masatoshi Kudo.
Cardiovasc Intervent Radiol, 2022 Feb 05; 45(4). PMID: 35119481    Free PMC article.
Systemic Therapy for Hepatocellular Carcinoma: Current Updates and Outlook.
Yinjie Fan, Hang Xue, Huachuan Zheng.
J Hepatocell Carcinoma, 2022 Apr 08; 9. PMID: 35388357    Free PMC article.
Review.
Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase II clinical trial.
Yongxiang Xia, Weiwei Tang, +28 authors, Xuehao Wang.
J Immunother Cancer, 2022 Apr 06; 10(4). PMID: 35379737    Free PMC article.
Extraction Optimization, Structural Characterization, and Anti-Hepatoma Activity of Acidic Polysaccharides From Scutellaria barbata D. Don.
Wenwen Su, Leilei Wu, +12 authors, Gaochen Song.
Front Pharmacol, 2022 Apr 22; 13. PMID: 35444545    Free PMC article.
Outcomes and Toxicities of Modern Combined Modality Therapy with Atezolizumab Plus Bevacizumab and Radiation Therapy for Hepatocellular Carcinoma.
Gohar Shahwar Manzar, Brian Sandeep De, +12 authors, Ethan Bernard Ludmir.
Cancers (Basel), 2022 Apr 24; 14(8). PMID: 35454808    Free PMC article.
Determinants of Survival and Post-Progression Outcomes by Sorafenib-Regorafenib Sequencing for Unresectable Hepatocellular Carcinoma.
I-Cheng Lee, Yee Chao, +6 authors, Yi-Hsiang Huang.
Cancers (Basel), 2022 Apr 24; 14(8). PMID: 35454919    Free PMC article.
Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma.
Nikolaos Machairas, Diamantis I Tsilimigras, Timothy M Pawlik.
Cancers (Basel), 2022 Apr 24; 14(8). PMID: 35454923    Free PMC article.
Review.
Chinese expert consensus on conversion therapy for hepatocellular carcinoma (2021 edition).
Hui-Chuan Sun, Jian Zhou, +77 authors, Alliance of Liver Cancer Conversion Therapy, Committee of Liver Cancer of the Chinese Anti-Cancer Association.
Hepatobiliary Surg Nutr, 2022 Apr 26; 11(2). PMID: 35464283    Free PMC article.
Review.
Molecular pathogenesis and systemic therapies for hepatocellular carcinoma.
Josep M Llovet, Roser Pinyol, +5 authors, Augusto Villanueva.
Nat Cancer, 2022 Apr 29; 3(4). PMID: 35484418    Free PMC article.
Review.
Frontline therapy for advanced hepatocellular carcinoma: an update.
Mehmet Akce, Bassel F El-Rayes, Tanios S Bekaii-Saab.
Therap Adv Gastroenterol, 2022 Apr 19; 15. PMID: 35432597    Free PMC article.
Review.
Rapidly Evolving Landscape and Future Horizons in Hepatocellular Carcinoma in the Era of Immuno-Oncology.
Sandra Mirie Kang, Lana Khalil, Bassel F El-Rayes, Mehmet Akce.
Front Oncol, 2022 Apr 19; 12. PMID: 35433430    Free PMC article.
Review.
Indirect Comparisons via Sorafenib for the Comparative Effectiveness of Two PD-1/PD-L1 Inhibitors to Treat Advanced Hepatocellular Carcinoma Patients without Prior Systemic Therapies.
Yawen Jiang, Dan Cai, Si Shi.
Clin Epidemiol, 2022 May 07; 14. PMID: 35520275    Free PMC article.
Proton beam radiotherapy combined with anti-PD1/PDL1 immune checkpoint inhibitors for advanced hepatocellular carcinoma.
Chung-Wei Su, Ming-Mo Hou, +7 authors, Chen-Chun Lin.
Am J Cancer Res, 2022 May 10; 12(4). PMID: 35530291    Free PMC article.
New insights into checkpoint inhibitor immunotherapy and its combined therapies in hepatocellular carcinoma: from mechanisms to clinical trials.
Haoer Jin, Sha Qin, +4 authors, Luqing Zhao.
Int J Biol Sci, 2022 May 12; 18(7). PMID: 35541908    Free PMC article.
Review.
Immune Checkpoint Inhibitors as Therapy to Down-Stage Hepatocellular Carcinoma Prior to Liver Transplantation.
Nitin N Katariya, Blanca C Lizaola-Mayo, +6 authors, Amit K Mathur.
Cancers (Basel), 2022 May 15; 14(9). PMID: 35565184    Free PMC article.
Review.