Neoadjuvant Immune Checkpoint Inhibitors for Hepatocellular Carcinoma

Overview

Journal NPJ Precis Oncol

Publisher Springer Nature

Specialty Oncology

Date 2025 Mar 6

PMID 40050446

Authors

Vinita Akula

Lily Chen

Yusuf Acikgoz

Katherine Klein

Betul Gok Yavuz

Lokman Cevik

Tarik Demir

Ashish Manne

Ilyas Sahin

Ahmed Kaseb

Elshad Hasanov

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC treatment is challenging; surgical resection is the primary curative treatment for early-stage disease, but recurrence rates are high. Immune checkpoint inhibitors (ICIs) are a promising neoadjuvant treatment that can reduce recurrence rates and mortality after surgery and achieve complete/partial responses. Clinical trials provide strong evidence for the efficacy and safety of ICI monotherapy for neoadjuvant HCC treatment.

References

Yavuz B, Hasanov E, Lee S, Mohamed Y, Curran M, Koay E . Current Landscape and Future Directions of Biomarkers for Immunotherapy in Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021; 8:1195-1207. PMC: 8478438. DOI: 10.2147/JHC.S322289. View

Ji J, Ha S, Lee D, Sankar K, Koltsova E, Abou-Alfa G . Predictive Biomarkers for Immune-Checkpoint Inhibitor Treatment Response in Patients with Hepatocellular Carcinoma. Int J Mol Sci. 2023; 24(8). PMC: 10144688. DOI: 10.3390/ijms24087640. View

Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre M . The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018; 359(6371):104-108. PMC: 6707353. DOI: 10.1126/science.aao3290. View

Claasen M, Sneiders D, Rakke Y, Adam R, Bhoori S, Cillo U . European Society of Organ Transplantation (ESOT) Consensus Report on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma. Transpl Int. 2023; 36:11648. PMC: 10533675. DOI: 10.3389/ti.2023.11648. View

Weissferdt A, Pataer A, Swisher S, Heymach J, Gibbons D, Cascone T . Controversies and challenges in the pathologic examination of lung resection specimens after neoadjuvant treatment. Lung Cancer. 2021; 154:76-83. DOI: 10.1016/j.lungcan.2021.02.014. View

Marron T, Fiel M, Hamon P, Fiaschi N, Kim E, Ward S . Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022; 7(3):219-229. PMC: 9901534. DOI: 10.1016/S2468-1253(21)00385-X. View

Liou H, Mody K, Boyle A, Keaveny A, Croome K, Burns J . Neoadjuvant Radiation Lobectomy and Immunotherapy for Angioinvasive HCC Resulting in Complete Pathologic Response. Hepatology. 2021; 74(1):525-527. DOI: 10.1002/hep.31675. View

Chiang C, Chan A, Chiu K, Kong F . Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy. Front Oncol. 2019; 9:1157. PMC: 6874138. DOI: 10.3389/fonc.2019.01157. View

Liao B, Liu L, Wei L, Wang Y, Chen L, Cao Q . Innovative Synoptic Reporting With Seven-Point Sampling Protocol to Improve Detection Rate of Microvascular Invasion in Hepatocellular Carcinoma. Front Oncol. 2021; 11:726239. PMC: 8599152. DOI: 10.3389/fonc.2021.726239. View

10.

Llovet J, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4):378-90. DOI: 10.1056/NEJMoa0708857. View

11.

Huo H, Wang X, Xu S, Niu X, Cheng L, Yuan Z . Transarterial chemoembolization plus camrelizumab is an effective and tolerable bridging therapy for patients with intermediate‑stage hepatocellular carcinoma: A pilot study. Oncol Lett. 2023; 26(5):465. PMC: 10534277. DOI: 10.3892/ol.2023.14052. View

12.

Tabrizian P, Jibara G, Shrager B, Schwartz M, Roayaie S . Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg. 2014; 261(5):947-55. DOI: 10.1097/SLA.0000000000000710. View

13.

Yau T, Park J, Finn R, Cheng A, Mathurin P, Edeline J . Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2021; 23(1):77-90. DOI: 10.1016/S1470-2045(21)00604-5. View

14.

Guo C, Zhang J, Huang X, Chen Y, Sheng J, Huang X . Preoperative sintilimab plus transarterial chemoembolization for hepatocellular carcinoma exceeding the Milan criteria: A phase II trial. Hepatol Commun. 2023; 7(3):e0054. PMC: 9916103. DOI: 10.1097/HC9.0000000000000054. View

15.

Ramon-Patino J, Schmid S, Lau S, Seymour L, Gaudreau P, Li J . iRECIST and atypical patterns of response to immuno-oncology drugs. J Immunother Cancer. 2022; 10(6). PMC: 9207898. DOI: 10.1136/jitc-2022-004849. View

16.

Zhou Y, Li A, Yu H, Wang Y, Zhang X, Qiu H . Neoadjuvant-Adjuvant vs Neoadjuvant-Only PD-1 and PD-L1 Inhibitors for Patients With Resectable NSCLC: An Indirect Meta-Analysis. JAMA Netw Open. 2024; 7(3):e241285. PMC: 10921251. DOI: 10.1001/jamanetworkopen.2024.1285. View

17.

Shindoh J, Hasegawa K, Inoue Y, Ishizawa T, Nagata R, Aoki T . Risk factors of post-operative recurrence and adequate surgical approach to improve long-term outcomes of hepatocellular carcinoma. HPB (Oxford). 2012; 15(1):31-9. PMC: 3533710. DOI: 10.1111/j.1477-2574.2012.00552.x. View

18.

El-Khoueiry A, Sangro B, Yau T, Crocenzi T, Kudo M, Hsu C . Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017; 389(10088):2492-2502. PMC: 7539326. DOI: 10.1016/S0140-6736(17)31046-2. View

19.

Zhu A, Finn R, Edeline J, Cattan S, Ogasawara S, Palmer D . Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018; 19(7):940-952. DOI: 10.1016/S1470-2045(18)30351-6. View

20.

Kuzuya T, Kawabe N, Hashimoto S, Miyahara R, Sawaki A, Nakano T . Early Changes in Alpha-Fetoprotein Are a Useful Predictor of Efficacy of Atezolizumab plus Bevacizumab Treatment in Patients with Advanced Hepatocellular Carcinoma. Oncology. 2021; 100(1):12-21. DOI: 10.1159/000519448. View