Outcome of sorafenib therapy in hepatocellular carcinoma. The multikinase inhibitor sorafenib is the first and only agent showing a survival benefit in these. Sorafenib effectiveness in advanced hepatocellular. It showed a 44% improvement in overall survival, with a median overall survival of. Although both the sharp and the asianpacific trials showed improved overall survival os for sorafenib, the magnitude of benefit was substantially less for asians, who have a higher prevalence of hepatitis b. Get emergency help right away if you get symptoms such as chest pain, shortness of breath, racing heartbeat, swelling in lower legs, feet and abdomen, feel lightheaded or faint, tiredness, nausea, vomiting, or sweat a lot. Sorafenib codeveloped and comarketed by bayer and onyx pharmaceuticals as nexavar, is a kinase inhibitor drug approved for the treatment of primary kidney cancer advanced renal cell carcinoma, advanced primary liver cancer hepatocellular carcinoma, flt3itd positive aml and radioactive iodine resistant advanced thyroid carcinoma. Call your doctor right away if you have chest pain or pressure, a fast. However, there are no headtohead trials comparing radiation therapy with yttrium90 microspheres and sorafenib in advanced hcc. Find out if sorafenib has any effect on patient reported outcomes. A phase iii study of sorafenib in patients with advanced.
Safety and efficacy of sorafenib in the treatment of hepatocellular. Sorafenib has shown antitumor activity in phase iii trials in patients with advanced hcc. Sorafenib prolonged time to progression vs placebo median ttp 24 weeks vs 12 weeks. Sorafenib in radioactive iodinerefractory, locally advanced. In the pivotal sorafenib hepatocellular carcinoma assessment randomized protocol sharp trial, sorafenibtreated patients had a median time to progression of 5. Sorafenib nexavar quelle place dans le traitement du. Learn about the efficacy of nexavar sorafenib in the clinical trial. Clinical trials using sorafenib tosylate national cancer.
Sorafenib hcc assessment randomized protocol sharp is a phase iii, multicenter, randomized, placebocontrolled trial. Sorafenib in advanced hepatocellular carcinoma nejm. Sorafenib for the treatment of unresectable hepatocellular carcinoma. Sorafenib codeveloped and comarketed by bayer and onyx pharmaceuticals as nexavar, is a kinase inhibitor drug approved for the treatment of primary kidney cancer advanced renal cell. Call your doctor right away if you have chest pain or pressure, a fast or abnormal heartbeat, shortness of breath, a big weight gain, swelling in the arms or legs, or very bad dizziness or passing out. Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib. New trials and results in systemic treatment of hcc journal of. The multikinase inhibitor sorafenib is the first and only agent showing a survival benefit in these patients. Expect from the usual adverse drug reactions sorafenib was found as a good choice for treating patients with advanced hcc. This is a randomized controlled trial that compared sorafenib nexavar to placebo in patients. Sorafenib is an oral multikinase inhibitor of vascular endothelial growth factor vegf. Sorafenib blocks the enzyme raf kinase, a critical component of the rafmekerk signaling pathway that.
Clinical trials are research studies that involve people. Tablets containing sorafenib tosylate 274 mg equivalent to 200 mg of sorafenib. M2 macrophages mediate sorafenib resistance by secreting. Nexavar tablets are available by prescription only and distributed through your healthcare professional hcp, as well as different types of pharmacies. Sharp of sorafenib plus best supportive care versus. Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis, and apoptosis. Sorafenib in patients with hepatocellular carcinomaresults of the. Before taking nexavar, tell your healthcare provider about all of your medical conditions, including if you. Advanced hepatocellular carcinoma hcc is a deadly disease with few systemic therapeutic options. Methods in this multicentre, randomised, doubleblind, placebocontrolled, phase 3 trial. Sorafenib in patients with hepatocellular carcinoma results of the. Out of 602 patients enrolled on the study, 325 had ecog ps 0 at. May 16, 2016 in the pivotal sorafenib hepatocellular carcinoma assessment randomized protocol sharp trial, sorafenib. Track 11 overview of the sharp trial results evaluating sorafenib versus placebo in patients with advanced hcc track 12 characteristics of sharp trial patient participants track child.
Owing to the format of the present study, patients. Adjuvant sorafenib for hepatocellular carcinoma after. Sorafenib effectiveness in advanced hepatocellular carcinoma. Mar 24, 2020 the sharp hcc study nct00105443 was a phase 3, international, multicenter, randomized, double blind, placebocontrolled trial in patients with unresectable hepatocellular carcinoma. Determine the pharmacokinetics pk in patients with liver cancer. Sorafenib in radioactive iodinerefractory, locally. Selective internal radiation therapy sirt also resulted in tumor response rates of 19 percent. Systemic therapy for advanced hepatocellular carcinoma. Hepatocarcinoma assessment randomized protocol sharp. This drug was approved in 2007 based on data from the sharp sorafenib hepatocellular carcinoma assessment randomized protocol study, which was a frontline study of patients with newly diagnosed advanced hcc who were randomized to sorafenib or placebo. Sorafenib blocks the enzyme raf kinase, a critical component of the rafmekerk signaling pathway that controls cell division and proliferation. Pdf systemic therapy for intermediate and advanced. This document file contains supplementary information. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the plateletderived growth factor receptor, and raf may be effective in hepatocellular carcinoma.
No effective therapy is available for advanced hepatocellular carcinoma. In this multicenter, phase 3, doubleblind, placebocontrolled trial, we randomly. The sharp hcc study nct00105443 was a phase 3, international, multicenter, randomized, double blind, placebocontrolled trial in patients with unresectable hepatocellular. Sorafenib in advanced hepatocellular carcinoma request pdf. Sorafenib associated adverse event led to dose reductions and interruptions in a subgroup of patients.
Sorafenib, a multikinase inhibitor, is the only approved systemic therapy for patients with unresectable or metastatic disease. Sirt is better tolerated than sorafenib, but doesnt increase overall survival in hcc ilc 2017. Get emergency medical help if you have signs of an allergic reaction hives, difficult breathing, swelling in your face or throat or a severe skin reaction. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endo. Sorafenib, a multitargeted kinase inhibitor, is the only drug that has demonstrated a survival benefit over supportive care in advanced hcc. In the landmark phase iii sharp trial including 602 hcc patients with mostly child pugh class a, sorafenib improved median overall survival mos compared to placebo 10. Highlights of prescribing information these highlights.
No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. Efficacy of sorafenib therapy in patients with advanced. There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. Find out if sorafenib prevents the growth of or shrinks liver tumors andor their metastases. Track 11 overview of the sharp trial results evaluating sorafenib versus placebo in patients with advanced hcc track 12 characteristics of sharp trial patient participants track childpugh score, bilirubin levels and the use of sorafenib in hcc track 14 case discussion. Optimal therapy for patients with hepatocellular carcinoma.
Together, these trials provided evidence for the effectiveness of sorafenib across a. The influence of ps on efficacy of sorafenib in the sharp trial was reported. Sorafenib in the treatment of advanced hepatocellular carcinoma. Relationship of ethnicity and overall survival in patients. Nexavar tablets are round, biconvex, red filmcoated tablets, debossed with the bayer cross on one. A phase iii study of sorafenib in patients with advanced hepatocellular carcinoma sharp the safety and scientific validity of this study is the responsibility of the study sponsor and. The sharp trial has demonstrated that sorafenib is effective in prolonging median survival and timetoprogression. Advanced hcc is a clinical challenge with limited treatment options.
The 602 patients in the sharp trial were stratified by tumor burden. In the pivotal sorafenib hepatocellular carcinoma assessment randomized protocol sharp trial, sorafenib treated patients had a median time to progression of 5. We undertook this phase 3, doubleblind, placebocontrolled. Haddad, md, summarizes the decision trial and the approval of sorafenib. Sorafenib for the treatment of advanced hepatocellular carcinoma.
The sharp trial until now, no effective systemic treatment options have been. Sorafenib therapy in advanced hepatocellular carcinoma. In this study we evaluate the efficacy and tolerability of sorafenib in an unselected patient population. Its approval was based on the results of the pivotal sharp. Placebo was the benchmark at the time because nothing else. Get emergency medical help if you have signs of an allergic reaction hives, difficult breathing, swelling in your face or throat or a severe skin reaction fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling. Approval of sorafenib therapy was based on the results of the sharp sorafenib hepatocellular carcinoma assessment randomized protocol trial and the asiapacific study. Sorafenib is the only agent to be fda approved for the firstline treatment.
Sirt is better tolerated than sorafenib, but doesnt increase. The actual life expectancy was not mentioned in the files, but was considered. Sorafenib is a synthetic compound targeting growth signaling and angiogenesis. Patient background in randomized controlled trials of sorafenib versus placebo in the sharp trial. All trials on the list are supported by nci ncis basic information about. In this randomized trial involving 602 patients with advanced hepatocellular carcinoma, sorafenib, a multikinase inhibitor o.
Request pdf sorafenib therapy in advanced hepatocellular carcinoma. In the pivotal sorafenib hepatocellular carcinoma assessment randomized protocol sharp trial, sorafenib treatedpatientshadamedian time to progression of 5. We found that, among patients in the sharp trial, sorafenib extended both os and ttp in patients with and without mvi andor ehs, compared with placebo. Heart problems like a type of abnormal heartbeat prolonged qt interval have happened with sorafenib. Its approval was based on the results of the pivotal sharp and sorafenib asiapacific ap trials in childpugh cp class a patients with advanced hcc, which showed significantly longer median overall survival os and time to radiological progression ttp with sorafenib 400 mg. The clinical trials on this list are studying sorafenib tosylate. Nexavar sorafenib dosing, indications, interactions. Moreover, sorafenib had the same safety profile, irrespective of the presence of mvi andor ehs. Find out if patients receiving sorafenib will live longer. Mar 11, 2020 heart problems like a type of abnormal heartbeat prolonged qt interval have happened with sorafenib. Evaluating sorafenib in veterans with advanced hepatocellular. Sirt is better tolerated than sorafenib, but doesnt.
Randomized protocol sharp, nct00105443 trial demonstrated an increase in median overall survival time and. Sorafenib caused embryofetal toxicities in animals at maternal exposures that were significantly lower than the human exposures at the recommended dose of 400 mg twice daily. Sorafenib nexavar, bay439006 sorafenib 400 mg was administered orally at a dose of 400 mg 2 x 200 mg tablets twice daily bid. A phase iii study of sorafenib in patients with advanced hepatocellular carcinoma sharp the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. In the sorafenib hepatocellular carcinoma assessment randomized protocol sharp trial 1, demonstrating an improvement in median.
Sorafenib in radioactive iodinerefractory, locally advanced or metastatic di. The sharp trial, conducted in 602 patients, was presented at last years asco meeting. Methods in this multicentre, randomised, doubleblind, placebocontrolled, phase 3 trial decision, we investigated sorafenib 400 mg orally twice daily in patients with radioactive iodinerefractory locally advanced or metastatic. Efficacy and safety of sorafenib in patients with advanced. Ncis basic information about clinical trials explains the types and phases of trials and how they are carried out. It showed a 44% improvement in overall survival, with a median overall survival of 10. This drug was approved in 2007 based on data from the sharp sorafenib hepatocellular carcinoma assessment randomized protocol study, which. Highlights of prescribing information these highlights do. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation.
Although both the sharp and the asianpacific trials showed improved overall survival os for sorafenib, the magnitude of benefit was substantially less for asians, who. Current and future systemic therapies for hepatocellular. In the sorafenib hepatocellular carcinoma assessment randomized protocol sharp, patients with unresectable advanced hcc with childpugh liver function class a and who had not received prior systemic therapy, received either oral sorafenib 400 mg twice daily or placebo until radiological and symptomatic progression. Sorafenib in dtc monograph addendum updated version may be found at. Relationship of ethnicity and overall survival in patients treated with sorafenib for advanced hepatocellular carcinoma background. Nexavar tablets are round, biconvex, red filmcoated tablets, debossed with the bayer cross on one side and 200 on the other side. Mar 15, 2017 sorafenib nexavar is currently the only systemic agent approved for use in hepatocellular carcinoma hcc. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant. Based on its mechanism of action and findings in animals, nexavar may cause fetal harm when administered to a pregnant woman. Both the sharp trial 7 conducted in western countries and the asianpacific trial8 demonstrated survival benefits of sorafenib versus placebo median os 10. Pdf sorafenib for the treatment of advanced hepatocellular.
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