Original Article

Efficacy of Second-Line Treatments After Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma and Related Prognostic Factors: A Multicenter Study by the Turkish Oncology Group (TOG)

Volume 36 · Issue 5 Publish Date: April 7, 2025
Nargiz Majidova ORCID Sendag Yaslıkaya ORCID Maral Martin Mıldanoglu ORCID Alper Coskun ORCID Duygu Ercan Uzundal ORCID Taha Koray Sahin ORCID Arif Akyildiz ORCID Sinem Akbas ORCID Ufuk Camanlı ORCID Elif Sahin ORCID Huseyin Atacan ORCID Ismail Bayrakcı ORCID Teoman Sakalar ORCID Ceren Mordag Cicek ORCID Damla Gunenc ORCID Nurullah İlhan ORCID Olcun Umit Unal Ozkan Alan ORCID Buket Hamitoglu ORCID Esra Ozen Engin ORCID Nadiye Sever ORCID Ali Kaan Guren ORCID Ahmet Unsal ORCID Murat Araz ORCID Bulent Erdogan ORCID Musa Barıs Aykan ORCID Fatih Selcukbiricik ORCID Deniz Can Guven ORCID Nuriye Ozdemir ORCID Ahmet Bilgehan Sahin ORCID Ahmet Bilici ORCID Ismail Oguz Kara ORCID Suayip Yalcın ORCID Osman Kostek ORCID
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Turkish Journal of Gastroenterology

Volume 36 · Issue 5

Pages: 293-301

History

Published Online: April 7, 2025

Creative Commons License

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

Copyright © 2025 Nargiz Majidova, Sendag Yaslıkaya, Maral Martin Mıldanoglu, Alper Coskun, Duygu Ercan Uzundal, Taha Koray Sahin, Arif Akyildiz, Sinem Akbas, Ufuk Camanlı, Elif Sahin, Huseyin Atacan, Ismail Bayrakcı, Teoman Sakalar, Ceren Mordag Cicek, Damla Gunenc, Nurullah İlhan, Olcun Umit Unal, Ozkan Alan, Buket Hamitoglu, Esra Ozen Engin, Nadiye Sever, Ali Kaan Guren, Ahmet Unsal, Murat Araz, Bulent Erdogan, Musa Barıs Aykan, Fatih Selcukbiricik, Deniz Can Guven, Nuriye Ozdemir, Ahmet Bilgehan Sahin, Ahmet Bilici, Ismail Oguz Kara, Suayip Yalcın, Osman Kostek

Nargiz Majidova ORCID
Division of Medical Oncology, VM Medical Park Maltepe Hospital, İstanbul, Türkiye
Sendag Yaslıkaya ORCID
Division of Medical Oncology, Çukurova University School of Medicine, Adana, Türkiye
Maral Martin Mıldanoglu ORCID
Division of Medical Oncology, Medipol University Hospital, İstanbul, Türkiye
Alper Coskun ORCID
Division of Medical Oncology, Uludağ University Faculty of Medicine, Bursa, Türkiye
Duygu Ercan Uzundal ORCID
Division of Medical Oncology, Gazi University, Ankara, Türkiye
Taha Koray Sahin ORCID
Division of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
Arif Akyildiz ORCID
Division of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
Sinem Akbas ORCID
Division of Medical Oncology, Koç University Hospital, İstanbul, Türkiye
Ufuk Camanlı ORCID
Division of Medical Oncology, İzmir Bozyaka Training and Research Hospital, İzmir, Türkiye
Elif Sahin ORCID
Division of Medical Oncology, Kocaeli City Hospital, Kocaeli, Türkiye
Huseyin Atacan ORCID
Division of Medical Oncology, Gülhane Training and Research Hospital, Ankara, Türkiye
Ismail Bayrakcı ORCID
Division of Medical Oncology, Trakya University, İstanbul, Türkiye
Teoman Sakalar ORCID
Division of Medical Oncology, Kahramanmaraş Necip Fazıl City Hospital, Kahramanmaraş, Türkiye
Ceren Mordag Cicek ORCID
Division of Medical Oncology, Pamukkale University Hospital, Denizli, Türkiye
Damla Gunenc ORCID
Division of Tulay Aktas Oncology, Ege University, İzmir, Türkiye
Nurullah İlhan ORCID
Division of Medical Oncology, İstanbul Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, İstanbul, Türkiye
Olcun Umit Unal
Division of Medical Oncology, Tepecik Training and Research Hospital, İzmir, Türkiye
Ozkan Alan ORCID
Division of Medical Oncology, Koç University Hospital, İstanbul, Türkiye
Buket Hamitoglu ORCID
Division of Medical Oncology, Eylül University Faculty of Medicine, İzmir, Türkiye
Esra Ozen Engin ORCID
Division of Medical Oncology, Sakarya University School of Medicine, Sakarya, Türkiye
Nadiye Sever ORCID
Division of Medical Oncology, Marmara University School of Medicine, İstanbul, Türkiye
Ali Kaan Guren ORCID
Division of Medical Oncology, Marmara University School of Medicine, İstanbul, Türkiye
Ahmet Unsal ORCID
Division of Medical Oncology, Gümüşhane State Hospital, Gümüşhane, Türkiye
Murat Araz ORCID
Division of Medical Oncology, Necmettin Erbakan University Meram Medical Faculty Hospital, Konya
Bulent Erdogan ORCID
Division of Medical Oncology, Trakya University, İstanbul, Türkiye
Musa Barıs Aykan ORCID
Division of Medical Oncology, Gülhane Training and Research Hospital, Ankara, Türkiye
Fatih Selcukbiricik ORCID
Division of Medical Oncology, Koç University Hospital, İstanbul, Türkiye
Deniz Can Guven ORCID
Division of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
Nuriye Ozdemir ORCID
Division of Medical Oncology, Gazi University, Ankara, Türkiye
Ahmet Bilgehan Sahin ORCID
Division of Medical Oncology, Uludağ University Faculty of Medicine, Bursa, Türkiye
Ahmet Bilici ORCID
Division of Medical Oncology, Medipol University Hospital, İstanbul, Türkiye
Ismail Oguz Kara ORCID
Division of Medical Oncology, Çukurova University School of Medicine, Adana, Türkiye
Suayip Yalcın ORCID
Division of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
Osman Kostek ORCID
Division of Medical Oncology, Marmara University School of Medicine, İstanbul, Türkiye
Majidova, N., Yaslıkaya, S., Mıldanoglu, M. M., Coskun, A., Ercan Uzundal, D., Sahin, T. K., … Kostek, O. (2025). Efficacy of Second-Line Treatments After Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma and Related Prognostic Factors: A Multicenter Study by the Turkish Oncology Group (TOG). Turkish Journal of Gastroenterology, 36(5), 293–301. https://doi.org/10.5152/tjg.2025.24784
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Abstract

Background/Aims: The treatment of hepatocellular carcinoma (HCC), which accounts for 90% of all liver cancers, is highly varied. The use of second-line treatments following progression on first-line atezolizumab and bevacizumab (Atez/Bev) for advanced HCC remains controversial. The aim of this study was to analyze the real-world clinical results of second-line treatments in progression after Atez/Bev and to determine the factors affecting prognosis.

Materials and Methods: Fifty-eight patients treated with second-line sorafenib, regorafenib, and cabozantinib for progression after first-line Atez/Bev for advanced/metastatic HCC from 20 centers in Türkiye between October 2020 and June 2024 were retrospectively analyzed. Responses were evaluated by Response criteria, specifically Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. Median overall survival (OS) and progression-free survival (PFS) were computed with the Kaplan–Meier method. The Cox regression model was utilized to analyze multivariate analyses.

Results: About 82.8% of the patients were male and the median age of the whole group was 62 (range, 18-78) years. All patients progressed after first-line Atez/Bev and were given second-line treatment. The most commonly used second-line treatment option was sorafenib (70.7%), followed by regorafenib (12.1%) and cabozantinib (10.3%). Both median PFS (4.1 months) and median OS (7.8 months) were longer in patients treated with sorafenib compared to other treatments. In univariate analyses, Child–Pugh score B, alpha-fetoprotein (AFP) levels (>200 ng/mL), extrahepatic spread, and Prognostic Nutritional Index (PNI) < 47.6 substantially raised the risk of overall mortality. Multivariate analysis showed that extrahepatic spread (HR (Hazard ratio): 0.41, P = .012), PNI level (HR: 0.24, P =.005), and AFP level (HR:1.97, P = .049) were independent predictors of OS.

Conclusion: Although second-line therapies after Atez/Bev show different degrees of efficacy, survival rates are consistent with the literature. Extrahepatic spread, AFP level, and PNI level are the main prognostic factors. In light of this information, personalized treatment strategies may improve outcomes for this challenging patient group.

 

Cite this article as: Majidova N, Yaslıkaya S, Mıldanoglu MM, et al. Efficacy of second-line treatments after atezolizumab and bevacizumab in advanced hepatocellular carcinoma and related prognostic factors: A multicenter study by the turkish oncology group (TOG). Turk J Gastroenterol. 2025;36(5):293-301.

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Article Info
Published In
Journal Turkish Journal of Gastroenterology
Volume / Issue Volume 36 · Issue 5
Pages 293-301
DOI 10.5152/tjg.2025.24784
History
Published Online April 7, 2025
License
Creative Commons License

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

Copyright
Copyright (c) 2025 Nargiz Majidova, Sendag Yaslıkaya, Maral Martin Mıldanoglu, Alper Coskun, Duygu Ercan Uzundal, Taha Koray Sahin, Arif Akyildiz, Sinem Akbas, Ufuk Camanlı, Elif Sahin, Huseyin Atacan, Ismail Bayrakcı, Teoman Sakalar, Ceren Mordag Cicek, Damla Gunenc, Nurullah İlhan, Olcun Umit Unal, Ozkan Alan, Buket Hamitoglu, Esra Ozen Engin, Nadiye Sever, Ali Kaan Guren, Ahmet Unsal, Murat Araz, Bulent Erdogan, Musa Barıs Aykan, Fatih Selcukbiricik, Deniz Can Guven, Nuriye Ozdemir, Ahmet Bilgehan Sahin, Ahmet Bilici, Ismail Oguz Kara, Suayip Yalcın, Osman Kostek
Affiliations
Nargiz Majidova ORCID
Division of Medical Oncology, VM Medical Park Maltepe Hospital, İstanbul, Türkiye
Sendag Yaslıkaya ORCID
Division of Medical Oncology, Çukurova University School of Medicine, Adana, Türkiye
Maral Martin Mıldanoglu ORCID
Division of Medical Oncology, Medipol University Hospital, İstanbul, Türkiye
Alper Coskun ORCID
Division of Medical Oncology, Uludağ University Faculty of Medicine, Bursa, Türkiye
Duygu Ercan Uzundal ORCID
Division of Medical Oncology, Gazi University, Ankara, Türkiye
Taha Koray Sahin ORCID
Division of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
Arif Akyildiz ORCID
Division of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
Sinem Akbas ORCID
Division of Medical Oncology, Koç University Hospital, İstanbul, Türkiye
Ufuk Camanlı ORCID
Division of Medical Oncology, İzmir Bozyaka Training and Research Hospital, İzmir, Türkiye
Elif Sahin ORCID
Division of Medical Oncology, Kocaeli City Hospital, Kocaeli, Türkiye
Huseyin Atacan ORCID
Division of Medical Oncology, Gülhane Training and Research Hospital, Ankara, Türkiye
Ismail Bayrakcı ORCID
Division of Medical Oncology, Trakya University, İstanbul, Türkiye
Teoman Sakalar ORCID
Division of Medical Oncology, Kahramanmaraş Necip Fazıl City Hospital, Kahramanmaraş, Türkiye
Ceren Mordag Cicek ORCID
Division of Medical Oncology, Pamukkale University Hospital, Denizli, Türkiye
Damla Gunenc ORCID
Division of Tulay Aktas Oncology, Ege University, İzmir, Türkiye
Nurullah İlhan ORCID
Division of Medical Oncology, İstanbul Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, İstanbul, Türkiye
Olcun Umit Unal
Division of Medical Oncology, Tepecik Training and Research Hospital, İzmir, Türkiye
Ozkan Alan ORCID
Division of Medical Oncology, Koç University Hospital, İstanbul, Türkiye
Buket Hamitoglu ORCID
Division of Medical Oncology, Eylül University Faculty of Medicine, İzmir, Türkiye
Esra Ozen Engin ORCID
Division of Medical Oncology, Sakarya University School of Medicine, Sakarya, Türkiye
Nadiye Sever ORCID
Division of Medical Oncology, Marmara University School of Medicine, İstanbul, Türkiye
Ali Kaan Guren ORCID
Division of Medical Oncology, Marmara University School of Medicine, İstanbul, Türkiye
Ahmet Unsal ORCID
Division of Medical Oncology, Gümüşhane State Hospital, Gümüşhane, Türkiye
Murat Araz ORCID
Division of Medical Oncology, Necmettin Erbakan University Meram Medical Faculty Hospital, Konya
Bulent Erdogan ORCID
Division of Medical Oncology, Trakya University, İstanbul, Türkiye
Musa Barıs Aykan ORCID
Division of Medical Oncology, Gülhane Training and Research Hospital, Ankara, Türkiye
Fatih Selcukbiricik ORCID
Division of Medical Oncology, Koç University Hospital, İstanbul, Türkiye
Deniz Can Guven ORCID
Division of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
Nuriye Ozdemir ORCID
Division of Medical Oncology, Gazi University, Ankara, Türkiye
Ahmet Bilgehan Sahin ORCID
Division of Medical Oncology, Uludağ University Faculty of Medicine, Bursa, Türkiye
Ahmet Bilici ORCID
Division of Medical Oncology, Medipol University Hospital, İstanbul, Türkiye
Ismail Oguz Kara ORCID
Division of Medical Oncology, Çukurova University School of Medicine, Adana, Türkiye
Suayip Yalcın ORCID
Division of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
Osman Kostek ORCID
Division of Medical Oncology, Marmara University School of Medicine, İstanbul, Türkiye
Cite this Article
Majidova, N., Yaslıkaya, S., Mıldanoglu, M. M., Coskun, A., Ercan Uzundal, D., Sahin, T. K., … Kostek, O. (2025). Efficacy of Second-Line Treatments After Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma and Related Prognostic Factors: A Multicenter Study by the Turkish Oncology Group (TOG). Turkish Journal of Gastroenterology, 36(5), 293–301. https://doi.org/10.5152/tjg.2025.24784
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