Effect of Trifluridine/Tipiracil Combination Depending on Patient Prognosis

Reminder of the RECOURSE Study

The double-blind phase III clinical trial included 800 patients with colorectal cancer pre-treated with standard therapy, who were subsequently randomized in a 2:1 ratio to the arm with trifluridine/tipiracil treatment or to receive a placebo.

The median overall survival (OS) in the active treatment arm reached 7.1 months, compared to 5.3 months in the control group (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.58–0.81; p < 0.001). The median progression-free survival (PFS) was 2.0 months with trifluridine and tipiracil treatment compared to 1.7 months with placebo (HR 0.48; 95% CI 0.41–0.57; p < 0.001).

Patient Prognosis

For the exploratory analysis presented in 2019 at the American Society of Clinical Oncology (ASCO) congress, patients included in the RECOURSE study were divided into prognostic groups. Patients with a good prognosis had a low tumor burden (i.e., < 3 metastatic lesions) and less aggressive disease (time from diagnosis to first metastasis ≥ 18 months). Within this group, a subgroup with the best prognosis was further profiled—patients without liver metastases. The group with an unfavorable prognosis had a higher tumor burden and a more aggressive course of the disease.

Results of the Analysis

In the subgroup of patients with the best prognosis, active treatment prolonged OS by 7.8 months (16.4 vs. 8.6 months; HR 0.47; 95% CI 0.29–0.74) and PFS by 3.5 months (5.4 vs. 1.9 months; HR 0.35; 95% CI 0.24–0.52). A statistically significant benefit of trifluridine/tipiracil in terms of OS and PFS was also observed in the group with good prognostic characteristics. Trifluridine/tipiracil prolonged OS by 2.5 months (9.3 vs. 6.8 months; HR 0.62; 95% CI 0.48–0.81) and PFS by 1.5 months (3.3 vs. 1.8 months; HR 0.39; 95% CI 0.31–0.50; see fig. 2). Patients treated with trifluridine/tipiracil maintained PS ECOG 0–1 significantly longer than patients with placebo. On average, ECOG PS deteriorated to grade ≥ 2 with active treatment 3.1 months later than with placebo (after 7.8 vs. 4.7 months; HR 0.53; 95% CI 0.41–0.69; p < 0.0001).

The analysis indicates that significantly better results in terms of OS and PFS extension are achieved with trifluridine/tipiracil treatment not only in the group with favorable prognosis but also in the group with unfavorable prognostic characteristics. Moreover, therapy with this drug led to the maintenance of good performance status in all prognostic groups.

Thus, regardless of the prognostic group in which the patient is classified, there is always a benefit from trifluridine/tipiracil treatment; however, this benefit is even more pronounced if the patient exhibits favorable prognostic characteristics.

Conclusion

The exploratory analysis of the RECOURSE study shows that trifluridine/tipiracil is an effective treatment that significantly prolongs mOS and mPFS in all patient subgroups in the third line of mCRC treatment and also allows for the maintenance of a very good performance status. Quality of life is a very significant parameter for heavily pre-treated patients. The greatest benefit of trifluridine/tipiracil was found in patients with the best prognosis. However, the results also demonstrate a significant benefit in patients with a worse prognosis.

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Sources:
1. Tabernero J., Sobrero A. F., Borg C. et al. Exploratory analysis of the effect of FTD/TPI in patients treated in RECOURSE by prognostic factors. J Clin Oncol 2019; 37 (4_suppl.): 677, doi: 10.1200/JCO.2019.37.4_suppl.677.
2. Mayer R. J., 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.