Biweekly TAS-102 Reduces Toxicity, Maintains Survival in Metastatic CRC

A retrospective analysis shows that trifluridine/tipiracil with or without bevacizumab given biweekly was favorable in those with colorectal cancer.

Biweekly dosing of trifluridine/tipiracil (TAS-102) reduced myelosuppression while maintaining survival outcomes with an improved toxicity profile in patients with refractory unresectable metastatic colorectal cancer (CRC), according to results from a retrospective analysis published in The Oncologist.1

The median overall survival (OS) of all patients who received TAS-102 at the biweekly dosing schedule was 9.2 months (95% CI, 6.5-12.1); the 1-year survival rate was 32.8% (95% CI, 21.4%-50.1%). The median progression-free survival (PFS) was 4.2 months (95% CI, 2.5-6.5).

Those who received TAS-102 in combination with bevacizumab (Avastin) experienced a median OS of 9.2 months (95% CI, 6.4-12.1) vs 8.8 months (95% CI, 5.4-not available [NA]) with TAS-102 monotherapy. The median PFS was 4.2 months (95% CI, 2.7-6.5) vs 3.2 months (95% CI, 2.3-8.2).

In the historical phase 3 RECOURSE trial (NCT01607957), the median OS and PFS with TAS-102 monotherapy were 7.1 months (95% CI, 6.5-7.8), with a 1-year survival rate of 27%, and 2 months (95% CI, 1.9-2.1), respectively.2 In the phase 3 SUNLIGHT trial (NCT04737187), the median OS and PFS were 7.5 months (95% CI, 6.3-8.6) and 2.4 months (95% CI, 2.1-3.2), respectively, with TAS-102 monotherapy; with TAS-102 plus bevacizumab, they were 10.8 months (95% CI, 9.4-11.8) and 5.6 months (95% CI, 4.5-5.9), respectively.3

“We’ve seen that this typical dosing schedule frequently causes significant bone marrow suppression, and patients often require dose reductions or treatment delays to recover. In other cases, patients have to use a medication called G-CSF, which helps to increase white blood cell counts,” stated lead study author Christopher G. Cann, MD, assistant professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, in a press release.4 “Use of this medication, however, can also cause [adverse] effects such as bone pain and other more serious complications.”

The analysis included a total of 61 patients with refractory metastatic CRC and appendiceal cancer who completed more than 12 days of TAS-102 therapy and underwent imaging every 8 to 12 weeks. The dosing regimen consisted of oral TAS-102 at 35 mg/m2, capped at 80 mg per dose, twice a day on days 1 to 5 and 15 to 19 of a 28-day cycle.

The median age of patients was 56.5 years (range, 30-80), the male-to-female patient ratio was 1.38:1, and 79% of patients had an ECOG performance status of 1. The median number of lines of prior therapy was 3.

Regarding adverse events (AEs), any-grade neutropenia was observed in 26.3% of patients who received TAS-102 monotherapy and 45.2% who received the combination; neutropenia of grade 3 or higher occurred in 15.8% and 16.7%. Any-grade anemia occurred in 52.6% vs 38.1%, respectively, and grade 3 or higher anemia occurred in 10.5% vs 7.1%. Any-grade thrombocytopenia occurred in 0% and 26.1%, and grade 3 or higher thrombocytopenia occurred in 0% and 2.4%.

In RECOURSE, neutropenia of any grade and grade 3 or higher occurred in 67% and 38% of those who received TAS-102 alone; in SUNLIGHT, it occurred in 51.2% and 32.1% with TAS-102 monotherapy and 62.2% and 43.1% with TAS-102 plus bevacizumab.

In RECOURSE, anemia of any grade and grade 3 or higher occurred in 77% and 18% of those who received TAS-102 alone; in SUNLIGHT, it occurred in 31.7% and 11.0% with TAS-102 monotherapy and 28.9% and 6.1% with TAS-102 plus bevacizumab.

In RECOURSE, thrombocytopenia of any grade and grade 3 or higher occurred in 42% and 5% of those who received TAS-102 alone; in SUNLIGHT, it occurred in 11.4% and 1.2% with TAS-102 monotherapy and 17.1% and 2.8% with TAS-102 plus bevacizumab.

“This retrospective analysis demonstrates a complementary dosing schedule of TAS-102 that results in similar therapeutic efficacy while reducing treatment-related toxicities in this palliative treatment setting,” wrote Cann and coauthors in the study.1 “Additional prospective, multicenter data [are] needed to validate our findings.”

References

1. Cann C, LaPelusa M, Cimino S, et al. Biweekly dosing of trifluridine-tipiracil reduces rates of myelosuppression while maintaining efficacy in patients with metastatic colorectal cancer. Oncologist. 2025;30(5):oyaf099. doi:10.1093/oncolo/oyaf099
2. Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909-1919. doi:10.1056/NEJMoa1414325
3. Prager GW, Taieb J, Fakih M, et al. Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer. N Engl J Med. 2023;388(18):1657-1667. doi:10.1056/NEJMoa2214963
4. Fox Chase Cancer Center researcher shows biweekly dose of TAS-102 reduces toxicity and remains effective for treatment of colorectal cancer. News release. Fox Chase Cancer Center. June 5, 2025. Accessed June 16, 2026. https://tinyurl.com/4e4tznwc