Complete Response under Sorafenib Treatment for Hepatocellular Carcinoma is Associated to Development of Dermatology Adverse Events

Background. Hepatocellular carcinoma is a relevant cause of mortality worldwide, mainly among patients who have a prior liver disease. In spite of clear recommendations regarding surveillance and screening methods, most patients are still diagnosed only when they are no longer candidates to curative treatment modalities, while others do not achieve the goals of such treatments, thus increasing the need of anticancer drugs. Moreover, when cirrhotic patients begin to receive these drugs, many types of adverse events are seen as a reason to withdrawal, even when there are findings suggesting a good response to the treatment. Case Summary. This case report is about a cirrhotic patient who received many types of treatment, from surgery and chemoembolization during early stages to first- and second-line systemic therapy when the disease turned to be advanced. Since he had no signs of liver dysfunction and suffered tumor progression during sorafenib treatment, regorafenib was initiated. The main findings that make this case important are the adverse events after taking this second-line agent, which would certainly be considered unacceptable and would lead to the drug withdrawal. The reasons why regorafenib was maintained are explained based on clinical and imaging findings, showing how this decision led to an excellent response. Conclusions. The knowledge of the main adverse events described in the pilot clinical trials can avoid unnecessary withdrawal of regorafenib. In addition, some clinical and imaging findings can be deemed as predictors of good response to tyrosine kinase inhibitors.

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Sorafenib treatment by Child–Pugh score in Latin American patients with hepatocellular carcinoma

Future Oncology ◽

10.2217/fon-2020-0323 ◽

2020 ◽

Vol 16 (31) ◽

pp. 2511-2520

Author(s):

Laura L de Guevara ◽

Lucy Dagher ◽

Vanessa MV Arruda ◽

Keiko Nakajima ◽

Masatoshi Kudo

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Latin American ◽

Treatment Option ◽

Real World ◽

Safety Profile ◽

Treatment Duration ◽

Sorafenib Treatment ◽

Safety And Efficacy ◽

Grade 3

Aim: To evaluate sorafenib treatment in Latin American patients with unresectable hepatocellular carcinoma in the real-world GIDEON study. Patients & methods: Sorafenib administration, safety and efficacy were analyzed by Child–Pugh status. Results: Of 90 evaluable patients (37% Child–Pugh A, 46% Child–Pugh B and 3% Child–Pugh C at study entry), 97% started sorafenib at 800 mg/day. Patients with Child–Pugh B7 had the longest median treatment duration of sorafenib (33.1 weeks). Sorafenib-related adverse events occurred in 58% of patients with Child–Pugh A (21% grade 3/4) and 46% with Child–Pugh B (7% grade 3/4). Conclusion: Sorafenib had a similar safety profile across patients with Child–Pugh A and B and is a treatment option for both groups.

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267 DERMATOLOGIC ADVERSE EVENTS WITHIN THE FIRST 60 DAYS OF SORAFENIB TREATMENT ARE ASSOCIATED WITH BETTER OVERALL SURVIVAL (OS) IN PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC)

Journal of Hepatology ◽

10.1016/s0168-8278(13)60269-x ◽

2013 ◽

Vol 58 ◽

pp. S113 ◽

Cited By ~ 1

Author(s):

M. Reig ◽

C. Rodriguez de Lope ◽

N. Llarch ◽

A. Forner ◽

F. Torres ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Adverse Events ◽

Sorafenib Treatment ◽

Dermatologic Adverse Events

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An investigation of the safety of continued treatment with sorafenib in patients with unresectable hepatocellular carcinoma after the first disease progression: Multicenter, open-label, phase II safety study.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.462 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 462-462

Author(s):

Noriyuki Akutsu ◽

Shigeru Sasaki ◽

Hideyasu Takagi ◽

Hiroyuki Kaneto ◽

Kazuhiko Yonezawa ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Disease Progression ◽

Treatment Options ◽

Line Treatment ◽

First Line ◽

Open Label ◽

Sorafenib Treatment ◽

First Line Therapy ◽

Unresectable Hepatocellular Carcinoma

462 Background: Randomized studies showed that sorafenib significantly improved outcome in patients with unresectable hepatocellular carcinoma (HCC). However, there is no clear evidence to support the safety and benefit of continued treatment of sorafenib beyond disease progression (PD) in patients with HCC treated with sorafenib. We prospectively evaluated the safety and efficacy of sorafenib beyond PD in patients with HCC whose disease has progressed after first-line treatment with sorafenib. Methods: Unresectable HCC patients with evaluable lesion were treated with sorafenib until 1st PD, followed by soafenib until 2nd PD. The primary endpoint of the study was the safety after 1st PD until 2nd PD. Secondary endpoints of the study were response rate (RR), disease control rate (DCR), time to first PD (TTP1), time to second PD during continued treatment (TTP2), overall survival (OS), and safety throughout the treatment period. Adverse event was evaluated as per The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated as per Modified Response Evaluation in Solid Tumors (mRECIST) criteria. The Kaplan–Meier method was used to determine TTP and OS. Results: Of 30 patients enrolled from 6 sites in Japan, 29 patients received sorafenib treatment, and one patient refused chemotherapy. Twenty patients continued sorafenib beyond PD. Grade 3/4 adverse events occurred less frequently during TTP2 than during TTP1. No critical events related to sorafenib were reported during TTP2. In the first-line therapy, 29 patients treated with sorafenib showed RR of 10.3%, DCR of 60.7% and median TTP1 of 102 days. Twenty patients who received continued sorafenib beyond PD and showed RR of 0%, DCR of 45%, and median TTP2 of 77 days. Median survival time was 306 days. Conclusions: Sorafenib beyond PD had acceptable tolerability and considerable efficacy. In the present conditions without second line treatment, sorafenib beyond PD might be one of the treatment options. Clinical trial information: UMIN000005818.

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Comparison of the frequency of adverse events requiring interventions determined by telephone follow up in hepatocellular carcinoma patients treated with sorafenib and lenvatinib.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.507 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 507-507

Author(s):

Koki Morishita ◽

Hidetaka Suzuki ◽

Junko Tauchi ◽

Misaki K Takeno ◽

Kohei Hayashi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Treatment Withdrawal ◽

Cancer Center ◽

First Line ◽

Sorafenib Treatment ◽

Number Of Patients ◽

Center Hospital ◽

Hand Foot Syndrome

507 Background: The REFLECT trial demonstrated that lenvatinib is non-inferior to sorafenib for first-line treatment of unresectable hepatocellular carcinoma (uHCC). However, no comparison of the frequency of adverse events (AEs) requiring interventions has been reported yet between uHCC patients receiving sorafenib and those receiving lenvatinib. At the National Cancer Center Hospital East, Japan, pharmacists conduct telephone follow-up (TF) during the first month after the start of treatment with sorafenib or lenvatinib in uHCC patients, for the purpose of detecting and treating AEs early. The aim of this study was to reveal the frequency of AEs requiring interventions between patients receiving sorafenib and those receiving lenvatinib, based on TF. Methods: The characteristics, AEs and contents of intervention by TF of 56 uHCC patients who had been started on treatment with sorafenib and lenvatinib were reviewed retrospectively. The study subjects were 33 patients initiated on sorafenib treatment and monitored by TF from March 2017 to March 2018 (Group S) and 23 patients initiated on lenvatinib treatment and monitored by TF from March 2018 to March 2019 (Group L). Results: The total numbers of TFs in Group S and Group L were 91 and 48, respectively. The rate of AEs requiring interventions was significantly higher in Group S as compared to Group L (Group S, 17.6% (16/91); Group L, 4.2% (2/48); p = 0.032). The frequencies of the interventions, including use of supportive treatments (A), withdrawal of sorafenib or lenvatinib (B), and medical examination (C), differed between the two groups (A/B/C: Group S, 8/5/3 times vs. Group L, 2/0/0 times). The most frequently observed AE that necessitated intervention in Group S was the hand-foot syndrome (HFS) (75.0%, 12/16). Conclusions: The frequency of interventions for AEs appears to be higher in uHCC patients receiving sorafenib than in those receiving lenvatinib. Although a great number of patients taking sorafenib had symptomatic AEs, such as HFS, early detection of the symptoms through TF contributed to prevention of treatment withdrawal on account of AEs.

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Apatinib as second-line therapy in Chinese patients with advanced hepatocellular carcinoma: A randomized, placebo-controlled, double-blind, phase III study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4507 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4507-4507 ◽

Cited By ~ 4

Author(s):

Qiu Li ◽

Shukui Qin ◽

Shanzhi Gu ◽

Xiaoming Chen ◽

Lizhu Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Hazard Ratio ◽

Phase Iii ◽

Chinese Patients ◽

Biological Behavior ◽

Advanced Hepatocellular Carcinoma ◽

Double Blind ◽

Sorafenib Treatment ◽

Advanced Hcc

4507 Background: Chinese patients (pts) account for more than 50% of hepatocellular carcinoma (HCC) cases in the world and have special features in etiology, biological behavior, treatment strategy and prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib, an inhibitor targeting vascular endothelial growth factor receptor-2, in Chinese pts with pretreated advanced HCC. Methods: In this randomized, placebo-controlled, double-blind, phase 3 trial done in 31 sites in China, pts with HCC who had received at least one line of systemic therapy (including sorafenib and oxaliplatin-based chemotherapy, which is another first-line standard-of-care in China) and had Child-Pugh liver function class A or B ≤7 points were enrolled. The pts were randomly assigned (2:1) to receive 750 mg apatinib orally once daily or placebo and stratified by ECOG performance status (0 or 1), previous sorafenib treatment (yes or no), and extrahepatic spread and/or macrovascular invasion (yes or no) in 28-day treatment cycles. The primary endpoint was overall survival (OS). Results: Between Apr 01, 2014 and May 03, 2017, 393 pts were randomized and received at least one dose of study treatment (261 in apatinib arm and 132 in placebo arm). The median OS was significantly longer with apatinib than that with placebo (8.7 months [95% CI 7.5-9.8] vs 6.8 months [95% CI 5.7-9.1]; hazard ratio 0.785 [95% CI 0.617-0.998]; p=0.0476). Pts in the apatinib arm also had prolonged median progression free survival (PFS) compared with those in the placebo arm (4.5 months [95% CI 3.9-4.7] vs 1.9 months [95% CI 1.9-2.0]; hazard ratio 0.471 [95% CI 0.369-0.601]; p˂0.0001). The objective response rate was 10.7% (95% CI 7.2-15.1) with apatinib versus 1.5% (95% CI 0.2-5.4) with placebo. Treatment-related adverse events (TRAEs) were reported in 250 (97.3%) pts in the apatinib arm and 92 (70.8%) pts in the placebo arm. The most common TRAEs of grade 3 and 4 were hypertension (71 [27.6%] pts in the apatinib arm vs 3 [2.3%] pts in the placebo arm), hand-foot syndrome (46 [17.9%] vs 0), decreased platelet count (34 [13.2%] vs 1 [0.8%]), and decreased neutrophil count (27 [10.5%] vs 0). 24 (9.3%) pts with apatinib and 13 (10.0%) pts with placebo died due to adverse events, and none were deemed treatment-related by investigators. Conclusions: Apatinib significantly prolonged OS and PFS in Chinese pts with pretreated advanced HCC, and was well tolerated with a manageable safety profile. Clinical trial information: NCT02329860 .

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