Comparison of FOLFOX/CAPOX and Sorafenib in Locally Advanced or Metastatic Hepatocellular Carcinoma

Abstract

Objectives: Liver cancer ranks third in terms of mortality worldwide. Sorafenib is a tyrosine kinase inhibitor that was approved for patients with advanced hepatocellular cancer (HCC). There are not many large-scale studies comparing sorafenib with chemotherapy. We planned to compare the effectiveness of sorafenib and chemotherapy in advanced-stage HCC patients. Materials and Methods: Patients over the age of 18, who were followed up with a diagnosis of advanced stage HCC in the Medical Oncology Department at Ankara University Faculty of Medicine between 2012 and 2022, who received sorafenib or FOLFOX/CAPOX treatment as first-line treatment, were included in the study. Patient and disease characteristics were recorded from the hospital database (Avicenna) and compared statistically. Results: Forty-four patients were included. The Eastern Cooperative Oncology Group performance status of all patients was 0-1. Nine (22.5%) patients had liver cirrhosis. The distribution of Child-Pugh scores was similar between groups (p=0.45). It was seen that 22 (50%) patients had stage A-B disease and 22 (50%) patients had stage C disease. It was recorded that 37 (84.1%) patients received sorafenib and 7 (15.9%) patients received FOLFOX/CAPOX treatment. Progression-free survival was measured as 2 months for the FOLFOX/CAPOX arm and 1 month for the sorafenib arm (p=0.96, log-rank). Overall survival was measured as 8.8 months in the FOLFOX/CAPOX arm and 6.3 months in the sorafenib arm (p=0.29, log-rank). Conclusion: No difference in survival was demonstrated between sorafenib and FOLFOX/CAPOX treatment. Multicenter and larger population studies are needed to elucidate the place of fluoropyrimidine and oxaliplatin combination in HCC treatment.

Keywords

• Hepatocellular carcinoma
• liver cancer
• chemotherapy
• sorafenib

Lokal İleri veya Metastatik Hepatoselüler Karsinomda FOLFOX/CAPOX ve Sorafenib Karşılaştırması

Abstract

Amaç: Karaciğer kanseri, akciğer ve kolorektal kanserden sonra dünya çapında mortalite açısından üçüncü sırada yer almaktadır. Sorafenib, 2007 yılında inoperabl hepatoselüler kanser (HCC) hastalarında onay almış bir tirozin kinaz inhibitörüdür. Sorafenibin kemoterapi ile kıyaslandığı geniş çaplı fazla sayıda çalışma olmadığı görülmektedir. Bu çalışmada ileri evre HCC hastalarında sorafenib ile kemoterapi etkinliğinin karşılaştırılması planlandı. Gereç ve Yöntem: Ankara Üniversitesi Tıp Fakültesi, Tıbbi Onkoloji bölümünde 2012-2022 arasında ileri evre HCC tanısı ile takip edilen, birinci basamak tedavide sorafenib veya FOLFOX/CAPOX tedavisi alan, 18 yaş üzerindeki hastalar çalışmaya dahil edildi. Hasta ve hastalık özellikleri hastane veritabanından (Avicenna) kaydedildi ve istatistiki olarak karşılaştırıldı. Bulgular: Çalışmaya 44 hasta dahil edildi. Tüm hastaların Doğu Kooperatif Onkoloji Grubu performans durumu 0-1 idi. Dokuz (%22,5) hastada karaciğer sirozu mevcuttu. Tümör evreleri değerlendirildiğinde 22 (%50) hastada evre A-B, 22 (%50) hastada evre C hastalık olduğu görüldü. Sistemik tedavilerde 37 (%84,1) hastanın sorafenib, 7 (%15,9) hastanın FOLFOX/CAPOX tedavisi aldığı kaydedildi. Child-Pugh skorlarının dağılımı gruplar arasında benzerdi (p=0,45). Progresyonsuz sağkalım FOLFOX/CAPOX kolu için 2 ay, sorafenib kolu için 1 ay olarak ölçüldü (p=0,96, log-rank). Genel sağkalım FOLFOX/CAPOX kolunda 8,8 ay, sorafenib kolunda ise 6,3 ay olarak ölçüldü (p=0,29, log-rank). Sonuç: Sorafenib ile FOLFOX/CAPOX tedavisi arasında sağkalım açısından fark gösterilemedi. Fluoropirimidin ve okzaliplatin kombinasyonunun HCC tedavisindeki yerinin aydınlatılması için çok merkezli ve daha geniş popülasyonlu çalışmalara gereksinim vardır.

Keywords

• Hepatoselüler karsinom
• karaciğer kanseri
• kemoterapi
• sorafenib

References

1. 1. Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022;77:1598-1606.
2. 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.
3. 3. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76:681-693.
4. 4. Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl ClinSurg. 1964;1:1-85.
5. 5. Abou-Alfa GK, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA. Journal of Clinical Oncology. 2022;40:379-379.
6. 6. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. New England Journal of Medicine. 2020;382:1894-1905.
7. 7. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. New England Journal of Medicine. 2008;359:378-390.
8. 8. Nagahama H, Okada S, Okusaka T, et al. Predictive factors for tumor response to systemic chemotherapy in patients with hepatocellular carcinoma. Jpn J Clin Oncol. 1997;27:321-324.

9. 9. Lyu N, Wang X, Li J-B, et al. Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: a biomolecular exploratory, randomized, phase III trial (FOHAIC-1). Journal of Clinical Oncology. 2022;40:468-480.
10. 10. Yau T, Park J-W, Finn RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022;23:77-90.
11. 11. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. The Lancet. 2018;391:1163-1173.
12. 12. Abou-Alfa GK, Shi Q, Knox JJ, et al. Assessment of treatment with sorafenib plus doxorubicin vs sorafenib alone in patients with advanced hepatocellular carcinoma. JAMA Oncol. 2019;5:1582-1588.
13. 13. Assenat E, Pageaux G-P, Thézenas S, et al. Sorafenib alone vs. sorafenib plus GEMOX as 1st-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial. Br J Cancer. 2019;120:896-902.
14. 14. Zheng K, Zhu X, Fu S, et al. Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib for hepatocellular carcinoma with major portal vein tumor thrombosis: a randomized trial. Radiology. 2022;303:455- 464.