Trifluridine/Tipiracil (FTD/TPI) in Metastatic Colorectal Cancer in Hong Kong: A Territory-Wide Cohort Study

Abstract

Introduction: Randomized phase III trials showed that using trifluridine/tipiracil (FTD/TPI) in patients with pre-treated metastatic colorectal cancer (mCRC) conferred survival benefit versus placebo. Here, we investigated the effectiveness and safety of FTD/TPI and sought to identify prognostic factors among the mCRC population in Hong Kong.

Methods: A non-interventional, retrospective, multicenter cohort study enrolled patients with mCRC who received FTD/TPI in seven public hospitals in Hong Kong between 2016 and 2020. Overall survival (OS) was the primary endpoint; treatment duration and occurrence of neutropenia were secondary endpoints. We also performed a post hoc analysis to identify factors influencing OS and treatment duration.

Results: Overall, 456 patients were included (median age, 64.0 years; 57.5% men). Approximately half (225/456; 49.3%) had RAS wild-type tumors; the median treatment duration was 12.4 weeks (95% confidence interval [CI] 11.1-13.1). Median OS was 7.59 months (95% CI 7.00-8.21). Overall, 289 (63.4%) patients developed neutropenia of any grade and 159 (34.9%) developed grade ≥ 3 neutropenia. Neutropenia at 1 month occurred in 193 (43.1%) patients. The use of granulocyte colony-stimulating factor for neutropenia was reported for 42 (9.2%) patients. The development of neutropenia, absolute neutrophil count decrease of ≥ 2 grades in 1 month, absence of liver metastasis, and RAS wild-type status were associated with significantly longer OS and, except for RAS wild-type status (not analyzed), longer treatment duration (p < 0.05 for all comparisons).

Conclusion: Our data show that treatment with FTD/TPI offers survival benefits in patients with refractory mCRC in Hong Kong consistent with randomized controlled trials and other real-world studies. Furthermore, the prognosis in patients receiving FTD/TPI appears to be significantly better in those who develop neutropenia, with RAS wild-type status, or those without liver metastases, despite a higher rate of dose reduction in the real-world setting.

Keywords: FTD/TPI; Metastatic colorectal cancer; Neutropenia; Prognostic factor; Real-world; TAS-102; Trifluridine/tipiracil.

Fig. 1

Patient flow diagram

Fig. 2

Kaplan–Meier curves for overall survival a in the total population; b by RAS mutation status; c in patients with or without liver metastasis; and d in patients with a ≥ 2-grade change from baseline ANC versus those who had a < 2-grade change at 1 month. Overall survival data were cut off on 7 November 2021. ANC absolute neutrophil count