Regorafenib (Stivarga) - colorectal cancer 1 Published 09 October 2023 1 SMC2562 regorafenib film-coated tablets (Stivarga®) Bayer Plc. 08 September 2023 The Scottish Medicines Consortium (SMC) has completed its assessment of the above product and advises NHS Boards and Area Drug and Therapeutic Committees (ADTCs) on its use in NHSScotland. The advice is summarised as follows: ADVICE: following a full submission assessed under the end of life and orphan equivalent medicine process regorafenib (Stivarga®) is accepted for use within NHSScotland. Indication under review: as monotherapy for the treatment of adult patients with metastatic colorectal
Regorafenib and sunitinib for treating advanced gastrointestinal stromal tumours ACE Technology Guidances A Singapore Government Agency Website SEARCH Who We Are Organisational Structure Advisory Committees Committees We Serve Careers at ACE Healthcare Professionals ACE Clinical Guidances (ACGs) ACE CUES ACE Technology Guidances ACE Horizon Scanning Patients & Community Asthma Resources Plain : * Regorafenib 40 mg tablet for treating patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumours (GISTs) who have been previously treated with imatinib mesylate. Subsidy status Regorafenib
Regorafenib and trifluridine/tipiracil for previously treated metastatic colorectal cancer ACE Technology Guidances A Singapore Government Agency Website SEARCH Who We Are Organisational Structure Advisory Committees Committees We Serve Careers at ACE Healthcare Professionals ACE Clinical Guidances (ACGs) ACE CUES ACE Technology Guidances ACE Horizon Scanning Patients & Community Asthma Resources : * Regorafenib 40 mg tablet for treating metastatic colorectal cancer that has been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and if RAS wild-type, an anti-EGFR therapy
Identification of differentially expressed mRNA/lncRNA modules in acutely regorafenib-treated sorafenib-resistant Huh7 hepatocellular carcinoma cells. The multikinase inhibitor sorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), but many patients become sorafenib-resistant (SR). This study investigated the efficacy of another kinase inhibitor, regorafenib
Imatinib alternating with regorafenib compared to imatinib alone for the first-line treatment of advanced gastrointestinal stromal tumor: The AGITG ALT-GIST intergroup randomized phase II trial. To determine if an alternating regimen of the tyrosine kinase inhibitors imatinib and regorafenib improved outcomes in patients with advanced gastrointestinal stromal tumors. ALTGIST (NCT02365441 ) was a randomized phase II study of standard treatment of imatinib (Arm A) compared with an experimental alternating regimen of imatinib and regorafenib (Arm B). Primary outcome was best objective tumor response (OTR) at nine months. Seventy-six eligible patients (Arm A 36, Arm B 40) enrolled were evaluable. Median follow-up was 46.0 months (range 6.5-64.6). Best responses and OTR were similar at 9 months
CHOP regulated by METTL14-m6A affects cell cycle arrest and regorafenib sensitivity in HCC cells. Regorafenib, a multi-targeted kinase inhibitor, has been used in the treatment of Hepatocellular carcinoma (HCC). The purpose of this study is to investigate the mechanism of Regorafenib in HCC. Regorafenib's impact on the sensitivity of HCC cells was assessed using CCK8. Differential gene expression analysis was performed by conducting mRNA sequencing after treatment with Regorafenib. The m6A methylation status of CHOP and differential expression of m6A methylation-related proteins were assessed by RIP and Western Blot. To explore the molecular mechanisms involved in the therapeutic effects of Regorafenib in HCC and the impact of METTL14 and CHOP on Regorafenib treatment, we employed shRNA
Regorafenib monotherapy or combined with an immune-checkpoint inhibitor as later-line treatment for metastatic colorectal cancer: a multicenter, real-world retrospective study in China. To evaluate the efficacy and safety of regorafenib monotherapy or in combination with immune-checkpoint inhibitor while treating Chinese patients with metastatic colorectal cancer (mCRC): a real-world study . The data of patients with metastatic colorectal cancer who received regorafenib-containing regimen as the third or later line treatment at ten Chinese hospitals from Aug 2017 to Jun 2020 were retrospectively analyzed, including dosing details, survival data as well as adverse events. Survival analysis was further performed for patients administrated with regorafenib monotherapy and combined
Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer. The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated
Circulating microRNA analysis in a prospective co-clinical trial identifies MIR652-3p as a response biomarker and driver of regorafenib resistance mechanisms in colorectal cancer. The multi-kinase inhibitor regorafenib has demonstrated efficacy in chemo-refractory metastatic colorectal cancer (mCRC) patients. However, lack of predictive biomarkers and concerns over significant toxicities hamper the use of regorafenib in clinical practice. Serial liquid biopsies were obtained at baseline and monthly until disease progression in chemo-refractory mCRC patients treated with regorafenib in a phase II clinical trial (PROSPECT-R n=40; NCT03010722) and in a multicentric validation cohort (n=241). Tissue biopsies collected at baseline, after 2 months and at progression in the PROSPECT-R trial were used
A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS-102 in irinotecan-refractory metastatic colorectal cancer patients. DNA methyltransferase inhibitors (DNMTi) have demonstrated benefit in reversing resistance to systemic therapies for several cancer types. In a phase II trial of guadecitabine and irinotecan compared to regorafenib or TAS-102 in pts with advanced mCRC refractory to irinotecan. Patients with mCRC refractory to irinotecan were randomized 2:1 to guadecitabine and irinotecan (Arm A) vs standard of care regorafenib or TAS-102 (Arm B) on a 28-day cycle. Between January 15, 2016 and October 24, 2018, 104 pts were randomized at four international sites, with 96 pts undergoing treatment, 62 in Arm A and 34 in Arm B. Median overall survival was 7.15
Real-world dosing of regorafenib and outcomes among patients with metastatic colorectal cancer: a retrospective analysis using US claims data. The randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims
Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial. Regorafenib has anti-tumor activity in patients with unresectable hepatocellular carcinoma (uHCC) with potential immunomodulatory effects, suggesting that its combination with immune checkpoint inhibitor may have clinically meaningful benefits in patients with uHCC. The multicenter, single-arm, phase 2 RENOBATE trial tested regorafenib-nivolumab as front-line treatment for uHCC. Forty-two patients received nivolumab 480 mg every 4 weeks and regorafenib 80 mg daily (3-weeks-on/1-week-off schedule). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints included safety
Association between sidedness and survival among chemotherapy refractory metastatic colorectal cancer patients treated with trifluridine/tipiracil or regorafenib. The impact of sidedness on survival of later-line treatment in patients with metastatic colorectal cancer (mCRC) is undetermined. This study aimed to investigate the association between sidedness and survival among chemotherapy refractory patients with mCRC treated with trifluridine/tipiracil (TAS-102) or regorafenib or both. Patients with mCRC treated with TAS-102 or regorafenib between 2015 and 2020 was retrospectively collected. Patients were stratified into TAS-102 first and regorafenib first, then subdivided into TAS-102 followed by regorafenib (T-R) and regorafenib followed by TAS-102 (R-T) groups. The oncologic outcomes
Phase 2 trial of regorafenib in recurrent or metastatic adenoid cystic carcinoma. There is a significant need for effective therapies to treat recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC). This study evaluated the multi-targeted, vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) regorafenib in patients with R/M ACC. Patients with progressive R/M ACC were treated with regorafenib until disease progression, consent withdrawal, or excessive toxicity. The primary endpoints were best overall response (BOR) and 6-month progression-free survival (PFS). Genomic and transcriptomic biomarker analyses were performed in tumors from trial participants. Thirty-eight patients were enrolled, including 7 (18%) patients with prior VEGFR-TKIs. No objective
Osteosarcoma cells depend on MCL-1 for survival, and osteosarcoma metastases respond to MCL-1 antagonism plus regorafenib in vivo. Osteosarcoma is the most common form of primary bone cancer, which primarily afflicts children and adolescents. Chemotherapy, consisting of doxorubicin, cisplatin and methotrexate (MAP) increased the 5-year osteosarcoma survival rate from 20% to approximately 60 % by the 1980s. However, osteosarcoma survival rates have remained stagnant for several decades. Patients whose disease fails to respond to MAP receive second-line treatments such as etoposide and, in more recent years, the kinase inhibitor regorafenib. BCL-2 and its close relatives enforce cellular survival and have been implicated in the development and progression of various cancer types. BH3-mimetics
Updated survival outcome of regorafenib, ipilimumab, and nivolumab in refractory microsatellite stable non-liver metastatic colorectal cancer: A phase I nonrandomized clinical trial. Combination regorafenib, ipilimumab, and nivolumab (RIN) was evaluated in a phase 1 nonrandomized study (NCT04362839) of refractory microsatellite stable (MSS) metastatic colorectal cancer. Promising antitumor
Regorafenib induces DNA damage and enhances PARP inhibitor efficacy in pancreatic ductal carcinoma. There is increasing interest in enhancing the response of the PARP inhibitor olaparib, which is currently approved for pancreatic ductal adenocarcinoma (PDAC) patients with defects in DNA damage repair associated with germline BRCA1/2 mutations. Moreover, agents that can mimic these defects in the absence of germline BRCA1/2 mutations are an area of active research in hopes of increasing the number of patients eligible for treatment with PARP inhibitors. The extent to which regorafenib, an FDA-approved tyrosine kinase inhibitor, can be used to enhance the efficacy of PARP inhibitors in PDAC cells without known BRCA1/2 mutations remains to be investigated. Comet assay, cell cycle analysis, western