Regorafenib monotherapy for previously treated metastatic. Costeffectiveness analysis of regorafenib for metastatic colorectal cancer daniel a. In the randomised, phase iii correct trial, regorafenib improved overall survival os versus placebo, with a hazard ratio hr of 0. The phase iii correct trial, exploring regorafenib, reported 6. Regorafenib doseoptimisation in patients with refractory. On the basis of these results and the high unmet need in this population of patients, the decision was made to proceed to a randomised phase 3 trial. Regorafenib is an orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. The recommended starting dose is 160 mg stivarga 4 40mg tablets taken orally once daily for the first 3 weeks, followed by a 1week treatment break. Regorafenib monotherapy for previously treated metastatic colorectal cancer correct.
Background in the international, phase iii, randomized, doubleblind correct trial, regorafenib significantly prolonged overall survival os versus placebo in patients with metastatic colorectal cancer mcrc that had progressed on all standard therapies. Safety and effectiveness of regorafenib full text view. Correct trial met its primary endpoint showing that the regorafenib group. Jan 26, 20 regorafenib monotherapy for previously treated metastatic colorectal cancer correct. The correct trial demonstrated statistically significant improvements in both overall survival and in progressionfree survival for regorafenib treatment patients over those receiving best supportive care alone, however there was inadequate tumor shrinkage among. The correct trial demonstrated an improved median overall survival os of 1. Regorafenib related teaes led to treatment discontinuation in 17% of patients. Full text evolution of regorafenib from bench to bedside in. Alberto sobrero, salvatore siena, alfredo falcone, marc ychou, yves humblet, olivier bouche, laurent mineur, carlo barone, antoine adenis.
Efficacy of regorafenib in metastatic colorectal cancer. Sep 12, 2014 background in the international, phase iii, randomized, doubleblind correct trial, regorafenib significantly prolonged overall survival os versus placebo in patients with metastatic colorectal cancer mcrc that had progressed on all standard therapies. The multikinase inhibitor regorafenib was shown to improve survival in patients with treatmentrefractory mcrc in the phase iii correct n 760 and concur n 204 trials. Regorafenib is an option for patients in turkey with treatmentrefractory mcrc.
Jan 22, 2014 it is the aim of this observational cohort study to further characterize safety and effectiveness of regorafenib in routine clinical practice setting. Regorafenib for patients with metastatic colorectal cancer. Phase iii correct trial of regorafenib in metastatic colorectal cancer mcrc eric van cutsem, md, phd university hospitals gasthuisbergleuven, leuven, belgium on behalf of. May 06, 2019 provides accurate and independent information on more than 24,000 prescription drugs, overthecounter medicines and natural products. Clinical trials look at new ways to prevent, detect, or treat disease. Apr 14, 2010 patients with metastatic colorectal cancer treated with regorafenib or placebo after failure of standard therapy the safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
Stivarga regorafenib dosing in the correct, phase 3 trial. All trials on the list are supported by nci ncis basic information about clinical trials explains the types and phases of trials and how they are carried out. In addition to mcrc, regorafenib is approved in gastrointestinal stromal tumours gist3 and. The objective of this randomized phase ii trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. Firstline singleagent regorafenib in frail patients with. In the correct study, fatal hepatic failure occurred in 1. Towards shedding some light on regorafenib treatment in.
Pdf evolution of regorafenib from bench to bedside in colorectal. Randomized phase iii trial of regorafenib in metastatic. Phase iii correct trial of regorafenib in metastatic. Clinical trials are research studies that involve people. Safety and effectiveness of regorafenib in patients with. The most common grade iii or higher drugrelated treatmentemergent adverse events teaes in the correct trial were handfoot skin reaction hfsr, fatigue, diarrhoea, hypertension and rash or desquamation. O012safety and effectiveness of regorafenib in patients with.
Clinical study efficacy overview stivarga regorafenib. Safety and efficacy of regorafenib in patients with treatment. The consign trial, carried out prospectively in more. Regorafenib was also studied in metastatic colorectal cancer in two large phaseiii randomized controlled trial, the correct trial and the concur trial the first on a western population and the second on an asian population. P261 pharmacokinetics of regorafenib in the phase 3 concur and correct trials in patients with metastatic colorectal cancer mcrc. Costeffectiveness analysis of regorafenib for metastatic. Results from the correct randomized study 11 showed that. A subsequent phase iii trial correct demonstrated significant clinical efficacy of regorafenib in patients with refractory or advanced mcrc. Clinical trials using regorafenib national cancer institute. We did the correct trial patients with metastatic colorectal cancer treated with regorafenib or. Regorafenib in metastatic colorectal cancer and advanced soft. It is indicated worldwide for patients with metastatic colorectal cancer mcrc. Healthcare resource utilization in the routine provision of care is becoming increasingly important from a health economics and outcomes research perspective.
Safety and effectiveness of regorafenib in patients with metastatic. The clinical trials on this list are studying regorafenib. Stivarga regorafenib tablets, for oral use initial u. Randomized phase iii trial of regorafenib in metastatic colorectal. Phase 3 trial of investigational compound regorafenib in. Of note, in the randomized controlled phaseiii grid trial, authors reported one patient with cardiac arrest.
Indeed, a randomized clinical trial in elderly andor frail patients with. Among patients who benefit, the response can be durable. Background in the international randomised phase 3 correct trial nct01103323, regorafenib significantly improved overall survival versus placebo in. We did the correct trial patients with metastatic colorectal cancer treated with regorafenib or placebo after failure of standard therapy to assess efficacy and safety of regorafenib in patients. Regorafenib is an important tool that can improve survival in patients with metastatic colorectal cancer. The overall incidence rate of regorafenib related hypertension has been reported to be as high as 44%, demonstrating the need for close monitoring and management. Stivarga can cause fetal harm when administered to a pregnant woman. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Regorafenib in chinese patients with metastatic colorectal. Regorafenib should be discontinued in patients with wound dehiscence. Firstline singleagent regorafenib in frail patients with metastatic. Treatment should continue until disease progression or until unacceptable toxicity. Phase 3 trial of investigational compound regorafenib in metastatic colorectal cancer meets primary endpoint of improving overall survival bayer trial stopped based on data from a preplanned.
Feb 25, 20 for the indication metastatic colorectal cancer, regorafenib was approved on the basis of the pivotal correct trial lancet. On november 29, 2018 the national institute for health and care excellence nice approved use of regorafenib in patients with advanced hepatocellular carcinoma who were previously treated with sorafenib. Regorafenib binds to and inhibits vascular endothelial growth factor receptors vegfrs 2 and 3, and ret, kit, pdgfr and raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. On the basis of the results of correct, regorafenib was approved for the. Background in the international randomised phase 3 correct trial nct01103323, regorafenib significantly improved overall survival versus placebo in patients with treatmentrefractory metastatic. Jun 26, 2018 regorafenib stivarga is an oral smallmolecule multiple kinase inhibitor. Regorafenib is an oral multikinase inhibitor that improves survival in patients with mcrc progressing on standard therapies. Patients with metastatic colorectal cancer treated with. However, safety data on regorafenib for mcrc in a larger number of patients were not available. If hair loss is a problem, refer to for the patient. P261 pharmacokinetics of regorafenib in the phase 3 concur. After the correct trial, two phase 3 trials consign, concur showed benefits compared to placebo.
Stivarga regorafenib tablets prescribing information. Conclusion the regorafenib safety profile and pfs in regard were consistent with the results of previous trials of regorafenib in mcrc. The randomised, phase iii concur trial confirmed the efficacy and safety of regorafenib in asian patients with mcrc. This post hoc analysis evaluated the efficacy and safety of regorafenib in japanese and nonjapanese subpopulations in the correct trial.
Fda approval was based on the results of the phase iii correct trial. Altogether, these three trials have defined the pattern of toxicity of regorafenib with hfsr, hypertension, fatigue and hypophosphatemia being the most frequent aes. The phase iii correct trial was conducted to evaluate efficacy and safety of regorafenib in patients with mcrc who had progressed after all approved. In regosarc, a phase ii study, regorafenib significantly prolonged progressionfree survival pfs in patients with nonadipocytic sts, with an ae profile similar to that seen in mcrc and gist. See full prescribing information for complete boxed warning. In the eu and usa it is indicated for patients with mcrc who have been previously treated with, or are not considered candidates for available therapies, including fluoropyrimidinebased chemotherapy, an antivegf therapy and, if ras. Regorafenib is an oral multikinase inhibitor that has been shown to block the activity of multiple protein kinases active in oncogenesis, tumor angiogenesis, as well as in the modulation of the tumor microenvironment. Results of a phase iii randomized, doubleblind, placebo. Signs of an infection such as fever over 100f or 38c by an oral thermometer. Severe and sometimes fatal hepatotoxicity has occurred in clinical trials. Median overall survival was 64 months in the regorafenib group versus 50 months in the placebo. Finally, the success of regorafenib in treating gist, the most common soft tissue sarcoma sts, has been extended to patients with other sts. Stivarga regorafenib label food and drug administration.
In the randomized, phase 3 correct and concur trials, regorafenib significantly improved overall survival os versus placebo in patients with mcrc who progressed on standard therapies. Ncis basic information about clinical trials explains the types and phases of trials and how they are carried out. Please ask your chemotherapy nurse or pharmacist for a copy. The rebecca study was a phase iv clinical trial and the concur study was a randomized trial conducted in asia with the same design as the correct study.
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