Preview

Meditsinskiy sovet = Medical Council

Advanced search

Combination of atezolizumab and bevacizumab in patients with inoperable hepatocellular cancer in real clinical practice

https://doi.org/10.21518/ms2023-426

Abstract

Introduction. In the structure of Russian cancer incidence, malignant neoplasms (MN) of the liver occupy 1.61%. Patients with initially unresectable hepatocellular cancer (HCC) or progressive HCC after local treatment methods, in the absence of contraindications, are subject to systemic therapy.

Aim. To evaluate the direct effectiveness and long-term results of treatment of patients with inoperable HCC with the combination of atezolizumab and bevacizumab in real clinical practice.

Materials and methods. A multicenter (7 centers) retrospective observational study was conducted. It includes 56 previously untreated patients and 12 pretreated patients with a confirmed diagnosis of HCC who were treated with atezolizumab and bevacizumab. The male to female ratio was 2:1, with an average age of 60 years. ECOG 0-1 was in 86.8%, Child-Pugh liver function A – in 76.5%, B – in 23.5%, macroscopic portal vein invasion – in 27.9%, extrahepatic spread – in 35.3%, AFP more than 400 IU/ml – in 38.2%.

Results. Use of the atezolizumab and bevacizumab regimen as a first line led to a partial response in 7 patients (12.5%), to stabilization in 39 (69.6%), to progression in 10 (17.9%). The disease control rate was 82.1%, median progression free survival (PFS) was 9.9 months (95% confidence interval (CI) 6.2-n/a). Median overall survival (OS) was not reached (95% CI 10.2-n/a). PFS was significantly influenced by the functional state of the liver according to the Child-Pugh scale. Median PFS in class A was 18.0 months, in class B – 5.6 months: HR 2.54; 95% CI 0.92–7.05; p = 0.03.

Conclusion. The atezolizumab and bevacizumab regimen in real clinical practice demonstrates tolerability of therapy and treatment results that are not inferior to the data obtained in the registration study. No new adverse events were identified.

About the Authors

V. V. Petkau
Sverdlovsk Regional Oncology Dispensary
Russian Federation

Vladislav V. Petkau - Cand. Sci. (Med.), Deputy Chief Physician for Drug Therapy, Sverdlovsk Regional Oncology Dispensary.

29, Sobolev St., Ekaterinburg, 620039



D. Yu. Shemetov
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Russian Federation

Dmitrii Yu. Shemetov - Head of the Day Patient Department of Antitumor Drug Therapy, Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine.

42, Blucher St., Chelyabinsk, 454087



K. O. Semenova
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Russian Federation

Kseniya O. Semenova - Oncologist, the Day Patient Department of Antitumor Drug Therapy, Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine.

42, Blucher St., Chelyabinsk, 454087



V. A. Chubenko
Saint Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncological) named after N.P. Napalkov
Russian Federation

Viacheslav A. Chubenko - Cand. Sci. (Med.), Head of the Department of Antitumor Drug Therapy No. 2 (Solid Tumors), Saint Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncological) named after N.P. Napalkov.

68а, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758



A. V. Sultanbaev
Bashkir State Medical University
Russian Federation

Alexander V. Sultanbaev - Cand. Sci. (Med.), Head of the Department of Antitumor Drug Therapy, Republican Clinical Oncology Dispensary.

73/1, Oktyabrya Ave., Ufa, Republic of Bashkortostan, 450054



K. V. Menshikov
Republican Clinical Oncology Dispensary; Bashkir State Medical University
Russian Federation

Konstantin V. Menshikov - Cand. Sci. (Med.), Associate Professor of the Department of Oncology with Courses in Oncology and Pathological Anatomy of the Institute of Postgraduate Education, Bashkir State Medical University; Oncologist of the Surgical Department No. 8, Republican Clinical Oncology Dispensary.

3, Lenin St., Ufa, Republic of Bashkortostan, 450008; 73/1, Oktyabrya Ave., Ufa, Republic of Bashkortostan, 450054



O. Yu. Novikova
Regional Clinical Center of Oncology
Russian Federation

Olga Yu. Novikova - Cand. Sci. (Med.), Deputy Chief Physician for Drug Therapy, Regional Clinical Center of Oncology.

164, Voronezhskoe Shosse, Khabarovsk, 680042



R. V. Orlova
St Petersburg State University; City Clinical Oncology Dispensary
Russian Federation

Rashida V. Orlova - Dr. Sci. (Med.), Head of the Department of Oncology, Faculty of Medicine, St Petersburg State University; Chief Specialist in Clinical Oncology, City Clinical Oncology Dispensary.

7/9, Universitetskaya Emb., St Petersburg, 199034; 3/5, 2nd Berezovaya Alley St., St Petersburg, 197022



N. V. Popova
City Clinical Oncology Dispensary
Russian Federation

Natalia V. Popova - Oncologist, Department of Antitumor Drug Therapy, City Clinical Oncology Dispensary.

3/5, 2nd Berezovaya Alley St., St Petersburg, 197022



A. S. Antipin
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Russian Federation

Artur S. Antipin - Oncologist, Oncological Day Hospital for Antitumor Drug Therapy (Chemotherapy), Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine.

42, Blucher St., Chelyabinsk, 454087



M. R. Mukhitova
Republican Clinical Oncology Dispensary named after Professor M.Z. Sigal
Russian Federation

Miliausha R. Mukhitova - Cand. Sci. (Med.), Head of Day Hospital No. 1, Republican Clinical Oncology Dispensary named after Professor M.Z. Sigal.

29, Siberian Tract St., Kazan, 420029



A. A. Tarkhanov
Sverdlovsk Regional Oncology Dispensary
Russian Federation

Andrey A. Tarkhanov - Head of the Department of X-ray Surgical Methods of Diagnosis and Treatment, Sverdlovsk Regional Oncology Dispensary.

29, Sobolev St., Ekaterinburg, 620039



K. E. Kiseleva
Sverdlovsk Regional Oncology Dispensary
Russian Federation

Kseniya E. Kiseleva - Oncologist of Outpatient Department, Sverdlovsk Regional Oncology Dispensary.

29, Sobolev St., Ekaterinburg, 620039



References

1. Каприн АД, Старинский ВВ, Шахзадова АО. Злокачественные новообра­ зования в России в 2021 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена; 2022. 252 с.

2. Каприн АД, Старинский ВВ, Шахзадова АО. Состояние онкологической помощи населению России в 2022 году. М.: МНИОИ им. П.А. Герцена; 2022. 239 с.

3. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6. https://doi.org/10.1038/s41572-020-00240-3.

4. Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022;76(3):681–693. https://doi.org/10.1016/j.jhep.2021.11.018.

5. Laface C, Fedele P, Maselli FM, Ambrogio F, Foti C, Molinari P et al. Targeted Therapy for Hepatocellular Carcinoma: Old and New Opportunities. Cancers (Basel). 2022;14(16):4028. https://doi.org/10.3390/cancers14164028.

6. Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022;23(1):77–90. https://doi.org/10.1016/S1470-2045(21)00604-5.

7. Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D et al. KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 201819(7):940–952. https://doi.org/10.1016/S1470-2045(18)30351-6.

8. Ang C, Klempner SJ, Ali SM, Madison R, Ross JS, Severson EA et al. Prevalence of established and emerging biomarkers of immune checkpoint inhibitor response in advanced hepatocellular carcinoma. Oncotarget. 2019;10(40):4018–4025. https://doi.org/10.18632/oncotarget.26998.

9. Hegde PS, Wallin JJ, Mancao C. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics. Semin Cancer Biol. 2018;52(2):117–124. https://doi.org/10.1016/j.semcancer.2017.12.002.

10. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al. IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894–1905. https://doi.org/10.1056/NEJMoa1915745.

11. 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):862–873. https://doi.org/10.1016/j.jhep.2021.11.030.

12. de Castro T, Jochheim LS, Bathon M, Welland S, Scheiner B, Shmanko K et al. Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience. Ther Adv Med Oncol. 2022;14:17588359221080298. https://doi.org/10.1177/17588359221080298.

13. Kulkarni AV, Krishna V, Kumar K, Sharma M, Patodiya B, Khan A et al. Safety and Efficacy of Atezolizumab-Bevacizumab in Real World: The First Indian Experience. J Clin Exp Hepatol. 2023;13(4):618–623. https://doi.org/10.1016/j.jceh.2023.02.003.

14. 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. Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: A multicenter analysis. Cancer Med. 2022;11(20):3796–3808. https://doi.org/10.1002/cam4.4763.

15. Breder VV, Bazin IZ, Balakhnin PV, Vershke ER, Kosyrev VYu, Ledin EV et al. Practical recommendations for the drug treatment of patients with malignant tumors of the liver and biliary system. Malignant Tumors. 2022;12(3s2-1):467–529. (In Russ.) https://doi.org/10.18027/2224-5057-2022-12-3s2-467-529.

16. Dzhanyan IА, Natrusova МV, Breder VV. Preliminary results of retrospective analysis Atezolizumab and Bevacizumab in first-line therapy of advanced HCC. Meditsinskiy Sovet. 2021;(4S)8–15. (In Russ.) https://doi.org/10.21518/2079-701X-2021-4S-8-15.

17. Menshikov KV, Sultanbaev AV, Musin SI, Menshikova IA, Abdeev RR, Sultanbaeva NI et al. Immunotherapy of advanced hepatocellular carcinoma: case report and literature review. Meditsinskiy Sovet. 2022;16(9):31–39. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-9-31-39.

18. Zhang CH, Cheng Y, Zhang S, Fan J, Gao Q. Changing epidemiology of hepatocellular carcinoma in Asia. Liver Int. 2022;42(9):2029–2041. https://doi.org/10.1111/liv.15251.

19. Rimassa L, Personeni N, Czauderna C, Foerster F, Galle P. Systemic treatment of HCC in special populations. J Hepatol. 2021;74(4):931–943. https://doi.org/10.1016/j.jhep.2020.11.026.

20. D’Alessio A, Fulgenzi CAM, Nishida N, Schönlein M, von Felden J, Schulze K et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. Hepatology. 2022;76(4):1000–1012. https://doi.org/10.1002/hep.32468.

21. Solimando AG, Susca N, Argentiero A, Brunetti O, Leone P, De Re V et al. Second-line treatments for Advanced Hepatocellular Carcinoma: A Systematic Review and Bayesian Network Meta-analysis. Clin Exp Med. 2022;22(1):65–74. https://doi.org/10.1007/s10238-021-00727-7.

22. Chen CT, Feng YH, Yen CJ, Chen SC, Lin YT, Lu LC et al. Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment. Hepatol Int. 2022;16(5):1199–1207. https://doi.org/10.1007/s12072-022-10392-x.

23. 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.

24. 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.

25. Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY et al. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020;38(3):193–202. https://doi.org/10.1200/JCO.19.01307.


Review

For citations:


Petkau VV, Shemetov DY, Semenova KO, Chubenko VA, Sultanbaev AV, Menshikov KV, Novikova OY, Orlova RV, Popova NV, Antipin AS, Mukhitova MR, Tarkhanov AA, Kiseleva KE. Combination of atezolizumab and bevacizumab in patients with inoperable hepatocellular cancer in real clinical practice. Meditsinskiy sovet = Medical Council. 2023;(22):41-48. (In Russ.) https://doi.org/10.21518/ms2023-426

Views: 302


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)