Sorafenib Continuation after First Disease Progression Could Reduce Disease Flares and Provide Survival Benefits in Patients with Hepatocellular Carcinoma: a Pilot Retrospective Study

Fu, Sirui; Zhang, Ying-Qiang; Li, Yong; Hu, Bao‐Shan; He, Xueling; Huang, Jianwen; Zhan, Meixiao; Lu, Ligong; Li, Jiaping

doi:10.7314/apjcp.2014.15.7.3151

Cited by 5 publications

(6 citation statements)

References 28 publications

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“…Our results showed that mALBI (2b or 3) at time of PD, decline of ECOG PS from baseline at time of PD, elevated AFP (≥100 ng/mL) at time of introducing LEN, PD pattern (appearance of new EHM), positive for HFSR (any grade), and continuing LEN beyond PD were significant prognostic factors for OS following PD. Although Fu et al [30] reported that BCLC-B (p = 0.002) and intrahepatic PD (p = 0.024) were significantly correlated with post-disease progression OS in SOR treatment, BCLC stage and intrahepatic PD patterns were not significant prognostic factors in the present study. Of course, it is reasonable that malignant potential of tumors (elevated tumor marker), worse hepatic function, and decline of ECOG PS were negative prognostic factors for survival.…”

Section: Discussioncontrasting

confidence: 79%

What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure?

et al. 2021

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Background/Aim: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). Methods: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. Results: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p < 0.001), and continuing LEN beyond PD (HR 0.297, p < 0.001). Conclusion: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.

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Section: Discussioncontrasting

confidence: 79%

What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure?

et al. 2021

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“…In addition, the efficacy of sorafenib as a first-line therapy for advanced HCC was reported in the SHARP (Sorafenib HCC Assessment Randomized Protocol) trial [7–10]. Specifically, sorafenib may provide survival benefits for patients with advanced HCC [11] as well as recurrent HCC following liver transplantation [12]. With the exception of HCC patients with Child-Pugh class B liver function [13, 14], sorafenib has a generally favorable safety profile [15–18].…”

Section: Introductionmentioning

confidence: 99%

Retrospective analysis of transarterial chemoembolization and sorafenib in Chinese patients with unresectable and recurrent hepatocellular carcinoma

et al. 2016

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We explored the hypothesis that sorafenib may improve the effect of transarterial chemoembolization (TACE) in patients with recurrent hepatocellular carcinoma (HCC) and that longer sorafenib duration was associated with additional survival benefits. In this retrospective, nested case-controlled study, 1126 cases of unresectable HCC were collected. Patients with unresectable disease treated with TACE+sorafenib (n=245) and TACE alone (n=245) and those with recurrence after surgery treated with TACE+sorafenib (n=127) and TACE alone (n=127) were identified and matched according to sex, age, and lesion size and number. The clinicopathological factors associated with survival were examined by univariate and multivariate analyses. The mean duration of sorafenib treatment was 10.8±10.51 months. Sorafenib significantly increased the median survival time as compared to TACE alone (unresectable HCC: 20.23 vs. 13.97 months, respectively; p=0.013 and recurrent HCC: 30.7 and 18.22 months, respectively; p=0.003). The survival of patients with unresectable HCC was associated with the presence of portal vein tumor thrombus (HR=1.47, p=0.004) and treatment method (TACE+sorafenib combination therapy; HR=0.72, p=0.003). For patients with recurrent HCC, the presence of extrahepatic metastasis (HR=1.71, p=0.012) and treatment method (TACE+sorafenib therapy; HR=0.60, p=0.002) also was associated with survival. For patients treated with TACE+sorafenib, multivariate analysis showed decreased hazard of death with longer duration of sorafenib treatment (HR=0.9, p<0.001). Thus, sorafenib plus TACE may provide survival benefits, which may be related with sorafenib treatment duration, particularly for patients with HCC recurrence. Further clinical studies are required to confirm these results and identify which patients are most likely to benefit from this therapeutic strategy.

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“…However, many patients in this study could not continue sorafenib treatment because of adverse events. Some previous studies have reported that sorafenib discontinuation may cause HCC flares, and patients who could continue sorafenib had better prognosis than patients who discontinued sorafenib (14,15,(24)(25)(26). Whereas our study also showed that patients who continued sorafenib ≥400 mg had good liver function and were candidates for regorafenib or other treatment; therefore, we analyzed predictive factors for continuation of sorafenib ≥400 mg.…”

Section: Discussionmentioning

confidence: 65%

High cholinesterase predicts tolerance to sorafenib treatment and improved prognosis in patients with transarterial chemoembolization refractory intermediate stage hepatocellular carcinoma

et al. 2019

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Although sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), the predictive factors sorafenib tolerance in intermediate-stage HCC cannot be accurately determined. The aim of the current study was to identify the predictive characteristics for the continuation of sorafenib treatment (≥400 mg) in patients with transarterial chemoembolization (TACE)-refractory intermediate HCC and to identify candidates for second-line sorafenib treatment. A total of 33 TACE-refractory intermediate patients with HCC that were treated with sorafenib, and who had reached progressive disease (PD), were analyzed in the present retrospective study. Of 33 patients, 6 patients (18.1%) were able to continue sorafenib treatment (≥400 mg) until PD, however, a total of 27 patients (71.9%) were unable to continue treatment (<400 mg). The current study compared the baseline characteristics parameters to sorafenib ≥400 mg and <400 mg using a logistic regression model. The overall survival (OS) of patients receiving sorafenib ≥400 mg treatment was significantly increased compared with patients receiving sorafenib treatment <400 mg [554.5 days (228-674) vs. 219 days (134-369); P= 0.0315). A univariate analysis was performed and indicated that Age (<75 years; P= 0.021), total cholesterol (>180 mg/dl; P= 0.026) and cholinesterase (ChE; ≥220 U/l; P= 0.024) were significant factors, and a multivariate analysis indicated that ChE (≥220 U/l) was a significant prognostic factor (HR: 11.9; 95% CI: 1.19-118.0; P=0.004). Both progression-free survival [279 (204-403) vs. 117.5 (63-197) days; P=0.0136] and OS [470 (277-679) vs. 171.5 (80-236) days; P=0.0004] were significantly increased in patients with ChE levels ≥220 U/l compared with patients exhibiting ChE levels <220 U/l. Baseline high value of ChE in intermediate-stage HCC predicts the ability to continue sorafenib treatment at ≥400 mg. High cholinesterase predicts tolerance to sorafenib treatment and improved prognosis in patients with transarterial chemoembolization refractory intermediate stage hepatocellular carcinoma

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Sorafenib Continuation after First Disease Progression Could Reduce Disease Flares and Provide Survival Benefits in Patients with Hepatocellular Carcinoma: a Pilot Retrospective Study

Cited by 5 publications

References 28 publications

What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure?

What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure?

Retrospective analysis of transarterial chemoembolization and sorafenib in Chinese patients with unresectable and recurrent hepatocellular carcinoma

High cholinesterase predicts tolerance to sorafenib treatment and improved prognosis in patients with transarterial chemoembolization refractory intermediate stage hepatocellular carcinoma

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