Comparison between Nivolumab and Regorafenib as Second-line Systemic Therapies after Sorafenib Failure in Patients with Hepatocellular Carcinoma
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. Materials and Methods: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. Results: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). Conclusion: Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.
Abstract
Purpose: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. Materials and Methods: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. Results: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). Conclusion: Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.
참고문헌 (30)
- Yang JD, "A global view of hepatocellular carcinoma : trends, risk, prevention and management", Nat Rev Gastroenterol Hepatol, 16, pp.589~604 (2019)
- Kim YA, "Socioeconomic burden of cancer in Korea from 2011 to 2015", Cancer Res Treat, 52, pp.896~906 (2020)
- Choi J, "Increasing burden of liver cancer despite extensive use of antiviral agents in a hepatitis B virus-endemic population", Hepatology, 66, pp.1454~1463 (2017)
- Bae H, "Effectiveness of hepatocellular carcinoma surveillance and an optimal surveillance interval : nationwide cohort of Korea", Yonsei Med J, 62, pp.758~766 (2021)
- Shin H, "Risk assessment of hepatocellular carcinoma development for indeterminate hepatic nodules in patients with chronic hepatitis B", Clin Mol Hepatol, 25, pp.390~399 (2019)
- Lee HW, "Liver diseases in South Korea : a pulse check of the public’s knowledge, awareness, and behaviors", Yonsei Med J, 63, pp.1088~1098 (2022)
- European Association for the Study of the Liver, "EASL clinical practice guidelines : management of hepatocellular carcinoma", J Hepatol, 69, pp.182~236 (2018)
- Sankar K, "Recent advances in the management of hepatocellular carcinoma", Clin Mol Hepatol, 30, pp.1~15 (2024)
- Hur MH, "Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis", Clin Mol Hepatol, 29, pp.763~778 (2023)
- Llovet JM, "Sorafenib in advanced hepatocellular carcinoma", N Engl J Med, 359, pp.378~390 (2008)
- Kudo M, "Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma : a randomised phase 3 non-inferiority trial", Lancet, 391, pp.1163~1173 (2018)
- Finn RS, "Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma", N Engl J Med, 382, pp.1894~1905 (2020)
- Bruix J, "Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment(RESORCE) : a randomised, double-blind, placebo-controlled, phase 3 trial", Lancet, 389, pp.56~66 (2017)
- Abou-Alfa GK, "Cabozantinib in patients with advanced and progressing hepatocellular carcinoma", N Engl J Med, 379, pp.54~63 (2018)
- Zhu AX, "Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations(REACH-2) : a randomised, double-blind, placebo-controlled, phase 3 trial", Lancet Oncol, 20, pp.282~296 (2019)
- El-Khoueiry AB, "Nivolumab in patients with advanced hepatocellular carcinoma(CheckMate 040) : an open-label, non-comparative, phase 1", 2dose escalation and expansion trial, 2017, pp.389, 2492~2502
- Kuo YH, "Nivolumab versus regorafenib in patients with hepatocellular carcinoma after sorafenib failure", Front Oncol, 11, pp.683341~ (2021)
- Lee CH, "Effectiveness of nivolumab versus regorafenib in hepatocellular carcinoma patients who failed sorafenib treatment", Clin Mol Hepatol, 26, pp.328~339 (2020)
- Choi WM, "Regorafenib versus nivolumab after sorafenib failure : real-world data in patients with hepatocellular carcinoma", Hepatol Commun, 4, pp.1073~1086 (2020)
- Reig M, "BCLC strategy for prognosis prediction and treatment recommendation : the 2022 update", J Hepatol, 76, pp.681~693 (2022)
- Heimbach JK, "AASLD guidelines for the treatment of hepatocellular carcinoma", Hepatology, 67, pp.358~380 (2018)
- Lee S, "Comparison of LI-RADS 2018 and KLCA-NCC 2018 for noninvasive diagnosis of hepatocellular carcinoma using magnetic resonance imaging", Clin Mol Hepatol, 26, pp.340~351 (2020)
- Llovet JM, "mRECIST for HCC : performance and novel refinements", J Hepatol, 72, pp.288~306 (2020)
- Kang SH, "KASL clinical practice guidelines : management of nonalcoholic fatty liver disease", Clin Mol Hepatol, 27, pp.363~401 (2021)
- Korean Association for the Study of the Liver(KASL), "KASL clinical practice guidelines for liver cirrhosis : varices, hepatic encephalopathy, and related complications", Clin Mol Hepatol, 26, pp.83~127 (2020)
- Silber JH, "Multivariate matching and bias reduction in the surgical outcomes study", Med Care, 39, pp.1048~1064 (2001)
- Xu S, "Use of stabilized inverse propensity scores as weights to directly estimate relative risk and its confidence intervals", Value Health, 13, pp.273~277 (2010)
- Korean Liver Cancer Association(KLCA), "2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma", Korean J Radiol, 23, pp.1126~1240 (2022)
- Kim K, "The effect of model for end-stage liver disease 3. 0 on disparities between patients with and without hepatocellular carcinoma in Korea", Yonsei Med J, 64, pp.647~657 (2023)
- Yau T, "Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib : the CheckMate 040 randomized clinical trial", JAMA Oncol, 6, pp.e204564~ (2020)