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Determinants of survival after sorafenib failure in patients with BCLC-C hepatocellular carcinoma in real-world practice.

Lee IC, Chen YT, Chao Y, Huo TI, Li CP, Su CW, Lin HC, Lee FY, Huang YH - Medicine (Baltimore) (2015)

Bottom Line: However, the survival benefit is short lived and survivals after progressive disease (PD) have not been well characterized.In general, patients with Mets only had better OS and PPS than those with portal vein invasion.Independent predictors of PPS include deteriorated performance status (HR = 7.680), deteriorated liver functions (HR = 5.603), bilirubin (HR = 2.114), early PD (HR = 6.109), and new extrahepatic lesion (HR = 1.804).

View Article: PubMed Central - PubMed

Affiliation: From the Division of Gastroenterology (I-CL, T-IH, C-PL, C-WS, H-CL, F-YL, Y-HH), Department of Medicine, Taipei Veterans General Hospital; Institute of Clinical Medicine (I-CL, Y-HH), National Yang-Ming University School of Medicine; Department of Nursing (Y-TC), Taipei Veterans General Hospital; Cancer Center (YC), Taipei Veterans General Hospital; and Institute of Pharmacology (T-IH), National Yang-Ming University School of Medicine, Taipei, Taiwan.

ABSTRACT
Sorafenib may improve progression-free survival (PFS) and overall survival (OS) of advanced hepatocellular carcinoma (HCC). However, the survival benefit is short lived and survivals after progressive disease (PD) have not been well characterized. This study aimed to evaluate the survival predictors of OS and postprogression survival (PPS) in advanced HCC patients receiving sorafenib treatment. Consecutive 149 HCC patients receiving sorafenib under National Health Insurance were retrospectively enrolled. All patients fulfilled the reimbursement criteria: Barcelona Clinic Liver Cancer stage C HCC with macroscopic vascular invasion or extrahepatic metastasis (Mets), and Child-Pugh class A. Radiologic assessment was performed at a 2-month interval using modified Response Evaluation Criteria in Solid Tumors. Patients who maintained Eastern Cooperative Oncology Group ≤2 and Child-Pugh class A at PD were assumed to be candidates for second-line treatment. During the median follow-up period of 7.5 months (range, 1.1-18.5), PD developed in 120 (80.5%) patients and 96 (64.4%) deaths occurred. The median PFS, OS, and PPS were 2.5, 8.0, and 4.6 months, respectively. In general, patients with Mets only had better OS and PPS than those with portal vein invasion. Independent predictors of OS include baseline performance status (hazard ratio [HR] = 1.956), tumor size (HR = 1.597), alpha-fetoprotein (HR = 1.869), discontinuation of sorafenib due to liver function deterioration (LD) (HR = 6.142), or concurrent PD and LD (HR = 2.661) and PD within 4 months (HR = 5.164). Independent predictors of PPS include deteriorated performance status (HR = 7.680), deteriorated liver functions (HR = 5.603), bilirubin (HR = 2.114), early PD (HR = 6.109), and new extrahepatic lesion (HR = 1.804). In 46 candidates for second-line trials, development of new extrahepatic lesion independently predicts poorer PPS (HR = 3.669). In conclusion performance status, liver functions, early disease progression, and progression pattern are important determinants of survival after sorafenib failure. These factors should be considered in clinical practice and second-line trial designs for patients with sorafenib failure.

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Related in: MedlinePlus

Kaplan–Meier analysis of overall and postprogression survivals in patients with different progression pattern. (A) Overall survival in patients with and without early disease progression. (B) Postprogression survival in 101 patients with image-confirmed disease progression. (C) Postprogression survival in 46 candidates of second-line treatment. NEL = new extrahepatic lesion.
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Figure 2: Kaplan–Meier analysis of overall and postprogression survivals in patients with different progression pattern. (A) Overall survival in patients with and without early disease progression. (B) Postprogression survival in 101 patients with image-confirmed disease progression. (C) Postprogression survival in 46 candidates of second-line treatment. NEL = new extrahepatic lesion.

Mentions: In univariate analysis, predictors of OS include ECOG performance status, concurrent VI and Mets, tumor size, serum AFP, bilirubin, albumin, AST levels, reasons for discontinuation of sorafenib, and PD within 4 months (Table 4). The median OS in patients who discontinued sorafenib due to PD only, LD only, concurrent PD and LD, and severe adverse events were 9.1, 5.6, 4.4, and 6.7 months, respectively (P < 0.001). Patients with early PD had significantly worse OS than those with PD after 4 months (median OS 4.9 vs 16.6 months, P < 0.001, Figure 2A). In multivariate analysis, ECOG performance statuses 1–2 (HR = 1.956, P = 0.004), tumor size >10 cm (HR = 1.597, P = 0.049), AFP >400 ng/mL (HR = 1.869, P = 0.008), discontinuation of sorafenib due to LD (HR = 6.142, P = 0.002) or concurrent PD and LD (HR = 2.661, P < 0.001), and PD within 4 months (HR = 5.164, P < 0.001) were independent factors associated with OS.


Determinants of survival after sorafenib failure in patients with BCLC-C hepatocellular carcinoma in real-world practice.

Lee IC, Chen YT, Chao Y, Huo TI, Li CP, Su CW, Lin HC, Lee FY, Huang YH - Medicine (Baltimore) (2015)

Kaplan–Meier analysis of overall and postprogression survivals in patients with different progression pattern. (A) Overall survival in patients with and without early disease progression. (B) Postprogression survival in 101 patients with image-confirmed disease progression. (C) Postprogression survival in 46 candidates of second-line treatment. NEL = new extrahepatic lesion.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554055&req=5

Figure 2: Kaplan–Meier analysis of overall and postprogression survivals in patients with different progression pattern. (A) Overall survival in patients with and without early disease progression. (B) Postprogression survival in 101 patients with image-confirmed disease progression. (C) Postprogression survival in 46 candidates of second-line treatment. NEL = new extrahepatic lesion.
Mentions: In univariate analysis, predictors of OS include ECOG performance status, concurrent VI and Mets, tumor size, serum AFP, bilirubin, albumin, AST levels, reasons for discontinuation of sorafenib, and PD within 4 months (Table 4). The median OS in patients who discontinued sorafenib due to PD only, LD only, concurrent PD and LD, and severe adverse events were 9.1, 5.6, 4.4, and 6.7 months, respectively (P < 0.001). Patients with early PD had significantly worse OS than those with PD after 4 months (median OS 4.9 vs 16.6 months, P < 0.001, Figure 2A). In multivariate analysis, ECOG performance statuses 1–2 (HR = 1.956, P = 0.004), tumor size >10 cm (HR = 1.597, P = 0.049), AFP >400 ng/mL (HR = 1.869, P = 0.008), discontinuation of sorafenib due to LD (HR = 6.142, P = 0.002) or concurrent PD and LD (HR = 2.661, P < 0.001), and PD within 4 months (HR = 5.164, P < 0.001) were independent factors associated with OS.

Bottom Line: However, the survival benefit is short lived and survivals after progressive disease (PD) have not been well characterized.In general, patients with Mets only had better OS and PPS than those with portal vein invasion.Independent predictors of PPS include deteriorated performance status (HR = 7.680), deteriorated liver functions (HR = 5.603), bilirubin (HR = 2.114), early PD (HR = 6.109), and new extrahepatic lesion (HR = 1.804).

View Article: PubMed Central - PubMed

Affiliation: From the Division of Gastroenterology (I-CL, T-IH, C-PL, C-WS, H-CL, F-YL, Y-HH), Department of Medicine, Taipei Veterans General Hospital; Institute of Clinical Medicine (I-CL, Y-HH), National Yang-Ming University School of Medicine; Department of Nursing (Y-TC), Taipei Veterans General Hospital; Cancer Center (YC), Taipei Veterans General Hospital; and Institute of Pharmacology (T-IH), National Yang-Ming University School of Medicine, Taipei, Taiwan.

ABSTRACT
Sorafenib may improve progression-free survival (PFS) and overall survival (OS) of advanced hepatocellular carcinoma (HCC). However, the survival benefit is short lived and survivals after progressive disease (PD) have not been well characterized. This study aimed to evaluate the survival predictors of OS and postprogression survival (PPS) in advanced HCC patients receiving sorafenib treatment. Consecutive 149 HCC patients receiving sorafenib under National Health Insurance were retrospectively enrolled. All patients fulfilled the reimbursement criteria: Barcelona Clinic Liver Cancer stage C HCC with macroscopic vascular invasion or extrahepatic metastasis (Mets), and Child-Pugh class A. Radiologic assessment was performed at a 2-month interval using modified Response Evaluation Criteria in Solid Tumors. Patients who maintained Eastern Cooperative Oncology Group ≤2 and Child-Pugh class A at PD were assumed to be candidates for second-line treatment. During the median follow-up period of 7.5 months (range, 1.1-18.5), PD developed in 120 (80.5%) patients and 96 (64.4%) deaths occurred. The median PFS, OS, and PPS were 2.5, 8.0, and 4.6 months, respectively. In general, patients with Mets only had better OS and PPS than those with portal vein invasion. Independent predictors of OS include baseline performance status (hazard ratio [HR] = 1.956), tumor size (HR = 1.597), alpha-fetoprotein (HR = 1.869), discontinuation of sorafenib due to liver function deterioration (LD) (HR = 6.142), or concurrent PD and LD (HR = 2.661) and PD within 4 months (HR = 5.164). Independent predictors of PPS include deteriorated performance status (HR = 7.680), deteriorated liver functions (HR = 5.603), bilirubin (HR = 2.114), early PD (HR = 6.109), and new extrahepatic lesion (HR = 1.804). In 46 candidates for second-line trials, development of new extrahepatic lesion independently predicts poorer PPS (HR = 3.669). In conclusion performance status, liver functions, early disease progression, and progression pattern are important determinants of survival after sorafenib failure. These factors should be considered in clinical practice and second-line trial designs for patients with sorafenib failure.

Show MeSH
Related in: MedlinePlus