Úloha imunoterapie pri liečbe hepatocelulárneho karcinómu

Download PDF English version

Authors: L. Balážová
Authors‘ workplace: Department of radiotherapy and oncology, East Slovakia Institute of Oncology, Košice
Published in: Gastroent Hepatol 2024; 78(5): 402-408
Category:
doi: https://doi.org/10.48095/ccgh2024402

Overview

Hepatocelulárny karcinóm (HCC) predstavuje najčastejšiu primárnu malignitu pečene, tvorí približne 75–80 % všetkých prípadov rakoviny pečene. Globálny výskyt hepatocelulárneho karcinómu sa zvyšuje v dôsledku rastúceho počtu základných ochorení, čo vytvára významnú rakovinovú záťaž a významnú klinickú výzvu v dôsledku jeho často neskorého prejavu a obmedzených účinných možností liečby. Inhibítory imunitného kontrolného bodu spôsobili revolúciu v prístupe k liečbe rôznych malignít. Pri liečbe pokročilého hepatocelulárneho karcinómu sa imunoterapia ukázala byť účinnejšia ako inhibítory tyrozínkinázy, ktoré boli možnosťou liečby už desaťročie. Klinické štúdie ako HIMALAYA a IMbrave150 preukázali významné prínosy prežitia a preukázali vyššiu účinnosť v porovnaní so sorafenibom. Napriek týmto sľubným výsledkom nie všetci pacienti s HCC reagujú na imunoterapiu rovnako. Je potrebné hľadať spoľahlivé prognostické a prediktívne biomarkery, ktoré môžu pomôcť predpovedať, ktorí pacienti budú s najväčšou pravdepodobnosťou profitovať z imunoterapie, a tým personalizovať liečbu a zlepšiť výsledky. Účelom tohto článku je poskytnúť súhrn klinických štúdií imunoterapie pre rôzne štádiá hepatocelulárneho karcinómu.

Klíčová slova:

rakovina pečene – hepatocelulárny karcinóm – inhibítory imunitných kontrolných bodov – imunoterapia – kombinované režimy

Sources

1. Sung H, Ferlay J, Siegel RL 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): 209–249. doi: 10.3322/caac.21660.

2. Rumgay H, Ferlay J, de Martel C et al. Global, regional and national burden of primary liver cancer by subtype. Eur J Cancer 2022; 161: 108–118. doi: 10.1016/j.ejca.2021.11.023.

3. Sagnelli E, Macera M, Russo A et al. Epidemiological and etiological variations in hepatocellular carcinoma. Infection 2020; 48 (1): 7–17. doi: 10.1007/s15010-019-01345-y.

4. Ducreux M, Abou-Alfa GK, Bekaii-Saab T et al. The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022. ESMO Open 2023; 8 (3): 101567. doi: 10.1016/j.esmoop.2023.101567.

5. Pons F, Varela M, Llovet JM. Staging systems in hepatocellular carcinoma. HPB (Oxford) 2005; 7 (1): 35–41. doi: 10.1080/13651820410024058.

6. Reig M, Forner A, Rimola J et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76 (3): 681–693. doi: 10.1016/j.jhep.2021.11.018.

7. Girardi DM, Sousa LP, Miranda TA et al. Systemic Therapy for Advanced Hepatocellular Carcinoma: Current Stand and Perspectives. Cancers (Basel) 2023; 15 (6): 1680. doi: 10.3390/cancers15061680.

8. Yu J, Li M, Ren B et al. Unleashing the efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma: factors, strategies, and ongoing trials. Front Pharmacol 2023; 14: 1261575. doi: 10.3389/fphar.2023.1261575.

9. Chan LL, Kung JWC, Chan SL. Neoadjuvant immunotherapy for early-stage hepatocellular carcinoma: the arts and science. ESMO Gastrointestinal Oncology 2023; 1: 15–20. doi: 10.1016/j.esmogo.2023.08.001.

10. Marron TU, Fiel MI, Hamon P et al. Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol 2022; 7 (3): 219–229. doi: 10.1016/S2468-1253 (21) 00385-X.

11. Kaseb AO, Hasanov E, Cao HST et al. Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma: a randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol 2022; 7 (3): 208–218. doi: 10.1016/S2468-1253 (21) 00427-1.

12. Qin S, Chen M, Cheng AL et al. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Lancet 2023; 402 (10415): 1835–1847. doi: 10.1016/S0140-6736 (23) 01796-8.

13. Wang K, Xiang YJ, Yu HM et al. Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial. Nat Med 2024; 30 (3): 708–715. doi: 10.1038/s41591-023-02786-7.

14. Knox J, Cheng A, Cleary S et al. A phase 3 study of durvalumab with or without bevacizumab as adjuvant therapy in patients with hepatocellular carcinoma at high risk of recurrence after curative hepatic resection or ablation: EMERALD-2. Ann Oncol 2019; 30 (4): IV59–IV60. doi: 10.1093/annonc/mdz155.216.

15. Vogel A, Zhu AX, Cheng A et al. Abstract No. 210 KEYNOTE-937 trial in progress: adjuvant pembrolizumab for hepatocellular carcinoma and complete radiologic response after surgical resection or local ablation. J Vasc Interv Radiol 2021; 32 (5): S92–S93. doi: 10.1016/j.jvir.2021.03.216.

16. Jimenez Exposito MJ, Akce M, Alvarez JLM et al. CA209-9DX: Phase III, randomized, double-blind study of adjuvant nivolumab vs placebo for patients with hepatocellular carcinoma (HCC) at high risk of recurrence after curative resection or ablation. Ann Oncol 2018; 29 (9): IX65. doi: 10.1093/annonc/mdy432.059.

17. Lencioni R, Kudo M, Erinjeri J et al. EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization. J Clin Oncol 2024; 42 (3): LBA432–LBA432. doi: 10.1200/JCO.2024.42.3_suppl.LBA432.

18. Abou-Alfa GK, Fan J, Heo J et al. 727TiP A randomised phase III study of tremelimumab (T) plus durvalumab (D) with or without lenvatinib combined with concurrent transarterial chemoembolisation (TACE) versus TACE alone in patients (pts) with locoregional hepatocellular carcinoma (HCC): EMERALD-3. Ann Oncol 2022; 33 (7): S874. doi: 10.1016/j.annonc.2022. 07.851.

19. Rimassa L, Finn RS, Sangro B. Combination immunotherapy for hepatocellular carcinoma. J Hepatol 2023; 79 (2): 506–515. doi: 10.1016/ j.jhep.2023.03.003.

20. Kudo M. Atezolizumab plus Bevacizumab Followed by Curative Conversion (ABC Conversion) in Patients with Unresectable, TACE-Unsuitable Intermediate-Stage Hepatocellular Carcinoma. Liver Cancer 2022; 11 (5): 399–406. doi: 10.1159/000526163.

21. Finn RS, Qin S, Ikeda M et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 2020; 382 (20): 1894–1905. doi: 10.1056/NEJMoa1915745.

22. Qin S, Chan SL, Gu S et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet 2023; 402 (10408): 1133–1146. doi: 10.1016/S0140-673 6 (23) 00961-3.

23. Abou-Alfa GK, Lau G, Kudo M et al. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid 2022; 1 (8): EVIDoa2100070. doi: 10.1056/EVIDoa21 00070.

24. Sangro B, Chan SL, Kelley RK et al. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Online. Ann Oncol 2024; 35 (5): 448–457. doi: 10.1016/j.annonc.2024.02.005.

25. Šafčák D, Dražilová S, Gazda J et al. Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Clinical Patterns, Outcomes, and Prognostic Factors for Overall Survival – A Retrospective Analysis of a Slovak Cohort. J Clin Med 2021; 10 (14): 3186. doi: 10.3390/jcm101 43186.

26. Šafčák D, Dražilová S, Gazda J et al. Alcoholic Liver Disease-Related Hepatocellular Carcinoma: Characteristics and Comparison to General Slovak Hepatocellular Cancer Population. Curr Oncol 2023; 30 (3): 3557–3570. doi: 10.3390/curroncol30030271.

27. Šafčák D, Dražilová S, Gazda J et al. Inflammatory Indexes as Prognostic Factors of Survival in Geriatric Patients with Hepatocellular Carcinoma: A Case Control Study of Eight Slovak Centers. J Clin Med 2022; 11 (14): 4183. doi: 10.3390/jcm11144183.

28. Šafčák D, HeCaRe, a multicentre prospective longitudinal study of prognostic factors in patients with hepatocellular carcinoma. 2024 [online]. Available from: https: //www.slovhep.sk/en/verejnost/clanok?uid=86f97ac025ee4f948e4754a6fa09ef71.

Submitted/Doručeno: 26. 8. 2024

Accepted/Přijato: 9. 9. 2024

Corresponding author

Lea Balážová, MD

Department of Radiotherapy and Oncology

East Slovakia Institute of Oncology

Rastislavova 43

041 91 Košice

lea.balazova@gmail.com