Exploratory study of TAS-102 combined with intermittent administration of fruquintinib in the treatment of third-line metastatic colorectal cancer.
Authors: Jiayu Niu, Huiqin Luo, Wenju Chen, Mengge Li, Ying Yan, Lulu Cao, Lihong Ke, Shusheng Wu, Huijun Xu, Huimin Li, Yifu He
Journal: Journal of Clinical Oncology (2025)

174 Background: Fruquintinib and TAS-102 are two globally recognized standard therapies for mCRC patients who have previously undergone standard chemotherapy. A phase II exploratory study suggested that the combination of TAS-102 and fruquintinib could prolong progression-free survival (PFS) and overall survival (OS) in these patients. However, the benefits are sometimes limited due to tolerability issues associated with continuous dosing. This study aimed to investigate the efficacy and safety of intermittent administration of TAS-102 combined with fruquintinib as a third-line treatment for mCRC patients. Methods: This open-label, single-arm, single-center, exploratory clinical trial enrolled mCRC patients who had failed at least two standard treatment regimens. Eligible patients received oral fruquintinib (3 mg, once daily, on days 1-5 and 8-12) and TAS-102 (35 mg/m², twice daily, on days 1-5) every two weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was objective response rate (ORR). Secondary endpoints included OS, PFS , DCR, and safety. Results: From August 2023 to September 2024, 26 eligible patients were enrolled. The median age of the patients was 58 years (range: 19-77), with 61.5% being female. RAS mutations were present in 57.7% of patients, 57.7% had left-sided colon or rectal cancer, 57.7% had liver metastases, and 76.9% had multiple metastases. As of September 10, 2024, 22 patients had undergone at least one tumor assessment, and 12 patients were still on treatment. Among them, 18.2% (4/22) achieved partial response , and 50% (11/22) had stable disease as the best response. Median PFS (mPFS) was 135 days (95% CI: 60.52-209.48). mPFS in RAS-mutant and RAS wild-type patients was 161 days (95% CI: 63.37-258.63) and 135 days (95% CI: 60.20-209.80), respectively, with ORRs of 25% and 12.5%. mPFS in patients with liver metastases (LM) and non-LM was 135 days (95% CI: 45.42-224.58) and 161 days (95% CI: 87.84-234.16), respectively, with ORRs of 14.3% and 25%. mPFS in patients with multiple metastases was 135 days (95% CI: 71.86-198.14), with an ORR of 17.6%. Median OS was not yet mature. Treatment-related adverse events (TRAEs) were generally manageable and tolerable. The most common hematological TRAEs (any grade, grades 3-4) included leukopenia (76.9%, 11.5%), neutropenia (73.1%, 11.5%), and anemia (53.8%, 7.7%). Non-hematological TRAEs were mostly grades 1-2, including anorexia (46.2%) and fatigue (19.2%). One case of grade 3 hypertension was reported. No treatment-related deaths were observed. Conclusion s: These preliminary results suggest that intermittent administration of TAS-102 in combination with fruquinitinib as a third-line treatment for patients with mCRC reduces hematological toxicity and is well tolerated, with encouraging clinical results. Clinical studies are ongoing. Clinical trial information: ChiCTR2300078241 .