A new retrospective study published in The Oncologist reports that a biweekly dosing schedule of trifluridine-tipiracil (TAS-102) offers a favorable balance between efficacy and reduced toxicity in patients with refractory metastatic colorectal cancer (mCRC) and appendiceal cancer. The findings have significant implications for treatment strategies in later-line settings, where tolerability often limits therapeutic options.
The study evaluated an alternative schedule—administering TAS-102 on days 1–5 and 15–19 of each 28-day cycle—aimed at preserving efficacy while minimizing adverse events. Among 61 patients (56 with mCRC, 5 with appendiceal cancer), the modified regimen resulted in a notable reduction in hematologic toxicity. Grade ≥3 neutropenia occurred in only 16.3% of patients, with just one case of grade 4 neutropenia, no reports of neutropenic fever, and no GCSF use. Grade ≥3 anemia was limited to 8.2% of patients.
Despite the improved safety profile, efficacy was maintained. In the mCRC subgroup, median progression-free survival (PFS) was 4.2 months and median overall survival (OS) was 9.2 months, comparable to outcomes reported in pivotal trials like RECOURSE and SUNLIGHT. Only eight patients required dose delays, and the cohort had a median Eastern Cooperative Oncology Group (ECOG) performance status of 1 with a median of three prior therapies.
Trifluridine-tipiracil, an oral agent combining a nucleoside analog (trifluridine) with a thymidine phosphorylase inhibitor (tipiracil), exerts anti-tumor effects by incorporating into DNA and inhibiting cancer cell replication. Tipiracil prevents the rapid degradation of trifluridine, enhancing its bioavailability and therapeutic impact.
A recent meta-analysis of seven studies involving 1,182 patients further supports the use of TAS-102 with bevacizumab, demonstrating significantly improved PFS (HR 0.52), OS (HR 0.61), objective response rate (RR 3.14), and disease control rate (RR 1.66), all with p-values <0.001. While neutropenia was more frequent in the combination arm, anemia was more common with TAS-102 monotherapy.
Colorectal cancer, one of the most prevalent and deadly malignancies globally, continues to pose a clinical challenge, particularly in advanced stages. As patients progress beyond first- and second-line treatments, effective and tolerable regimens become increasingly essential.
The current findings support the feasibility of a biweekly TAS-102 regimen as a more patient-friendly option that maintains therapeutic benefit while improving tolerability. This approach may broaden treatment access for patients with compromised performance status and inform the design of future clinical trials exploring novel combination strategies in advanced colorectal and appendiceal cancers.
Reference
- Christopher Cann, Michael LaPelusa, Sarah Cimino, Victoria Cancelliere, Elizabeth Dow-Hillgartner, Zhiguo Zhao, Dustin Deming, Cathy Eng, Biweekly dosing of trifluridine-tipiracil reduces rates of myelosuppression while maintaining efficacy in patients with metastatic colorectal cancer, The Oncologist, Volume 30, Issue 5, May 2025, oyaf099.
- Peeters, M., Cervantes, A., Moreno Vera, S., & Taieb, J. (2018). Trifluridine/Tipiracil: An Emerging Strategy for the Management of Gastrointestinal Cancers. Future Oncology, 14(16), 1629–1645.
- Aquino de Moraes, F.C., Dantas Leite Pessôa, F.D., Duarte de Castro Ribeiro, C.H. et al. Trifluridine–tipiracil plus bevacizumab versus trifluridine–tipiracil monotherapy for chemorefractory metastatic colorectal cancer: a systematic review and meta-analysis. BMC Cancer 24, 674 (2024)