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Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer.

ABSTRACT: Colorectal cancer is one of the most common tumors worldwide and at least 50 % of patients with this disease develop metastases. In this setting, additional treatment options are needed for patients presenting disease progression after exhausting all standard therapies. Regorafenib is an orally administered multikinase inhibitor which has been shown to provide survival benefits to patients with metastatic colorectal cancer (mCRC). Although most adverse events (AEs) associated with regorafenib may resolve within the first 8 weeks of treatment, some of them may require dose reduction or treatment interruption. Overall, while remaining aware of the safety profile of regorafenib and how to manage the most common toxicities related to its use, this drug should be considered a new standard of care for patients with pretreated mCRC. This review addresses practical aspects of its use, such as dosing, patient monitoring, and management of the most common regorafenib-related AEs.

SUBMITTER: Sastre J

PROVIDER: S-EPMC4194027 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer.

Sastre J J Argilés G G Benavides M M Feliú J J García-Alfonso P P García-Carbonero R R Grávalos C C Guillén-Ponce C C Martínez-Villacampa M M Pericay C C

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 20140916 11

Colorectal cancer is one of the most common tumors worldwide and at least 50 % of patients with this disease develop metastases. In this setting, additional treatment options are needed for patients presenting disease progression after exhausting all standard therapies. Regorafenib is an orally administered multikinase inhibitor which has been shown to provide survival benefits to patients with metastatic colorectal cancer (mCRC). Although most adverse events (AEs) associated with regorafenib ma ...[more]

PMID: 25223744

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Project description:IntroductionRegorafenib was recently approved for patients with pretreated advanced colorectal cancer (aCRC), despite a moderate improvement of the patients' outcome, and significant toxicities. Based on previous studies showing that early fluorodeoxyglucose-positron emission tomography (FDG-PET)-based metabolic response assessment (MRA) might adequately select patients unlikely to benefit from treatment, the RegARd-C trial uses early MRA to identify likely non-responders to regorafenib in a population of patients with aCRC and guide a comprehensive evaluation of genomic and epigenetic determinants of resistance to treatment.Methods and analysisRegARd-C is a multicentric prospective study. Its primary objective is to identify non-benefitters from regorafenib given at 160 mg/day, 3 weeks out of 4 in a population of patients with pretreated aCRC. Baseline PET is repeated at day 14 of the first treatment course. MRA is blinded for the investigators. Overall survival (OS) is the primary end point and will be correlated with metabolic parameters and (epi)genetic alterations assessed from tumour and serial blood samples. A target sample size of 105 evaluable patients (70 as derivation set and 35 as validation set), is considered as sufficient to validate an expected HR for OS of metabolic responders compared to metabolic non-responders significantly <1 (with 80% power and 1-sided 5% α in case of a true HR≤0.59 and a responders rate of 47%).Ethics and disseminationThe study was approved by the Institut Jules Bordet's competent ethics committee and complies with the Helsinki declaration or the Belgian laws and regulations, whichever provides the greatest protection for the patient, and follows the International Conference on Harmonisation E 6 (R1) Guideline for Good Clinical Practice, reference number CPMP/ICH/135/95. The protocol and the trials results, even inconclusive, will be presented at international oncology congresses, and published in peer-reviewed journals. Genomic and epigenetic data will be made available in public open data sets.Trial registration numbersEudraCT number: 2012-005655-16; ClinicalTrials.gov number: NCT01929616.

Project description:Regorafenib is an orally administered multikinase inhibitor that has been approved for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Even though regorafenib significantly improved survival in two international phase 3 trials (CORRECT and CONCUR), a high rate of treatment-related toxic effects and dose modifications were observed with a modest benefit. The aim of this study was to provide information concerning the efficacy, safety, and cost of regorafenib in patients with mCRC in clinical practice.We retrospectively reviewed patients treated with regorafenib monotherapy for unresectable mCRC in five Franche-Comté cancer hospitals (France). The primary end point was overall survival. Secondary end points were safety and descriptive cost analyses of patients treated with regorafenib in clinical practice. Another aim of this study was to assess the impact of regorafenib prescription on the risk of hospitalization in real-life practice.From January 2014 to August 2014, 29 consecutive patients were enrolled. Patients were heavily pretreated and were refractory to standard chemotherapies. The primary tumor sites were the colon and the rectum for 55% and 45% of patients, respectively. Fifteen patients (51%) harbored an RAS mutation. Eastern Cooperative Oncology Group - Performance Status (PS) was 0-1 for 86% of patients and 2 for 14% of patients. Nineteen patients (66%) initially received reduced doses of 120 or 80 mg/day. The median duration of treatment was 2.5 months (range, 0.13-11.4 months). Treatment-related adverse events occurred in 86% of patients. The most frequent adverse events of any grade were fatigue (35%), diarrhea (20%), and hand-foot skin reaction (20%). Grade 3 or 4 treatment-related adverse events occurred in 10 patients (35%). Three patients (10%) were admitted to hospital due to drug-related severe adverse events. The mean cost of patient management with regorafenib for the duration of treatment was 9908 ± 8191€, and median cost was 7917€ (Interquartile range (IQR) 4469-13,042). The median overall survival was six months (95% confidence interval, five to eight months).The safety and efficacy of regorafenib in heavily pretreated mCRC patients was comparable, in our study, to prospective and retrospective trials. Toxic effects were mostly manageable in an outpatient setting. Regorafenib itself represented the most important (93%) part of supported costs. Even though most side effects were manageable in an outpatient setting, severe adverse events occurred from hospitalization in 10% of patients. These data should be confirmed in a larger real-life-based cohort. Identification of predictive biomarkers is needed for mCRC patient selection for regorafenib treatment.

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Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer.

Publications

Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer.

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