Related Experiment Video
Updated: Jul 19, 2025
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian
Javier Martin-Broto1,2,3, Claudia Valverde4, Nadia Hindi5,6,7
1Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain. jmartin@atbsarc.org.
Background:
Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST.
Methods:
Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment.
Results:
From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST.
Conclusions:
Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST.
Trial Registration:
ClinicalTrials.gov Identifier: NCT02638766.
Insights
Regorafenib shows promising activity as an initial treatment for advanced KIT and PDGFRα wild-type gastrointestinal stromal tumors (KP-wtGIST). This therapy demonstrated a high disease control rate, particularly in SDH-deficient subtypes.
Area of Science:
- Oncology
- Gastrointestinal Oncology
- Molecular Oncology
Background:
- Approximately 15% of adult GIST patients have tumors wild-type for KIT and PDGFRα genes (KP-wtGIST).
- KP-wtGIST often exhibits SDH deficiencies, indolent behavior, and resistance to imatinib.
- Oncogenic drivers in KP-wtGIST include HIF1α overexpression or BRAF mutations, suggesting targeted therapy potential.
Purpose of the Study:
- To evaluate the efficacy of regorafenib as upfront therapy for advanced KP-wtGIST.
- To assess the disease control rate (DCR) of regorafenib in this patient population.
Main Methods:
- An international phase II trial included adult patients with advanced KP-wtGIST confirmed by NGS.
- Patients received regorafenib 160 mg daily for 21 days every 28 days.
- The primary endpoint was DCR at 12 weeks, assessed centrally via RECIST 1.1.
Main Results:
- The study enrolled 15 patients; 30 were identified as KP-wtGIST initially.
- The 12-week DCR was 86.7% by central assessment.
- Tumor shrinkage was observed in 60% of patients, with 13% partial responses and 87% stabilization; SDH-deficient GIST showed better outcomes.
Conclusions:
- Regorafenib demonstrates favorable activity in advanced KP-wtGIST, comparing well with other tyrosine kinase inhibitors.
- Regorafenib should be considered as an upfront therapy option for advanced KP-wtGIST.
- The SDH-deficient GIST subset particularly benefits from regorafenib treatment.
More Related Videos
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Related Concept Videos
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...