SUNRISE-CRC: a randomized phase II study of high-dose intermittent sunitinib versus trifluridine/tipiracil in metastatic colorectal carcinoma
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Patients with metastatic colorectal cancer often have poor or short responses to currently available therapies. Drug repurposing with alternative dosing schedules may offer unexpected clinical benefit, even for agents that previously failed for this indication. METHODS: We explored a high-dose treatment strategy for sunitinib, assessing its potential for both cancer cell killing and inducing immunogenic cell death in patient-derived tumor organoids (PDTOs) of metastatic colorectal cancer (mCRC). In a randomized clinical trial, we studied the efficacy of high-dose intermittent sunitinib (700 mg once every 2 weeks) in patients with advanced CRC compared to standard therapy with trifluridine/tipiracil. The primary outcome measure was progression-free survival (PFS); secondary outcomes included overall survival, safety and tolerability, quality of life, and exploratory biomarker analyses. RESULTS: While high, intermittent dosing was found to effectively kill PDTOs in vitro, no support for immunogenic cell death was found. In our clinical trial, among a total of 63 evaluable patients, median PFS was 2.8 months (95% CI 0.9-4.7) for the investigation arm compared to 1.9 months (95% CI 1.6-2.3) for the trifluridine/tipiracil group (P = .78, HR 1.22; 95% CI 0.73-2.04). The trial was halted prematurely due to toxicities: in particular, hemorrhage, fever and gastrointestinal adverse events. CONCLUSION: High-dose intermittent sunitinib treatment did not improve PFS for patients with heavily pretreated mCRC compared to standard 3rd or 4th-line treatment with trifluridine/tipiracil, whereas significant toxicity was observed. In addition, this approach provoked no relevant immunological responses in vitro, discouraging further research for potential combinations with immunotherapeutics. IDENTIFIER: NCT03909724.
Source: The Oncologist
Authors: Jorien B E Janssen, Kirti K Iyer, Sophie L Gerritse, Eline Janssen, Elske C Gootjes, Mariette Labots, Tineke E Buffart, Miriam L Wumkes, Joeri A J Douma, Mirte M Streppel, Laurien M Buffart, Marianne A Jonker, Erik van den Hombergh, Nielka P van Erp, Jan Paul Medema, Daniele V F Tauriello, Dennis Poel, Henk M W Verheul
Institutions: Radboud University Nijmegen, Radboud University Medical Center, Erasmus MC, Erasmus MC Cancer Institute, Amsterdam University Medical Centers, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Jeroen Bosch Ziekenhuis, The Netherlands Cancer Institute, Amphia Ziekenhuis, Oncode Institute, University of Amsterdam
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,852
Award: G1833149535
OpenAlex ID: W4414370367