Safety profile of trifluridine/tipiracil monotherapy in clinical practice: results of the German compassionate-use program for patients with metastatic colorectal cancer

Stefan Kasper,Meinolf Karthaus,Mohammad-Reza Rafiyan,Alexander Stein,Christian Müller,Martin Fuchs,Jens Kisro,Armin Schulz-Abelius

doi:10.1186/s12885-018-5063-5

Abstract

BackgroundTrifluridine/tipiracil (TAS-102, Lonsurf®), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine, FTD) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride, TPI) presents a new treatment option for metastatic colorectal cancer (mCRC) patients refractory or intolerant to standard therapies. FTD/TPI was approved in the European Union (EU) in April 2016 and launched on the German market in August 15, 2016.MethodsWe investigated the characteristics of patients (pts) with mCRC treated with FTD/TPI at 118 centers in Germany from January 12 to August 14, 2016 and analyzed the safety in a clinical real-world setting.ResultsIn Germany, a total of 226 mCRC patients were included into a compassionate-use-program (CUP) and received FTD/TPI. For 45.5% of patients (n = 101), 253 adverse events (AE) were documented, most of them drug-related (n = 135). From January 12 (2016) to March 2 (2017), 124 serious adverse events (SAE) were reported (74 drug related). The most common serious adverse drug reactions (SADR) were leukopenia (12 events), neutropenia (8 events), anemia (7 events), diarrhea and nausea (5 events each) (observation period January 12 2016 to October 7 2016). In total, 122 patients (54%) discontinued FTD/TPI treatment, mostly due to progression (n = 75) followed by AEs (n = 21), deaths (n = 16), and non-specified reasons (n = 16). Interestingly, 12 patients with ECOG PS ≥2 achieved up to 3 cycles of FTD/TPI and in this patient population only 3 treatment discontinuations due to AEs were documented and the safety profile was comparable to the entire population.ConclusionThe patient characteristics as well as the safety profile of FTD/TPI documented in the German CUP were consistent with those reported in the pivotal trial RECOURSE without unexpected safety signals.

Highlights

IntroductionTrifluridine/tipiracil (TAS-102, Lonsurf®), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine, FTD) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride, TPI) presents a new treatment option for metastatic colorectal cancer (mCRC) patients refractory or intolerant to standard therapies
Trifluridine/tipiracil (TAS-102, Lonsurf®), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue with a thymidine phosphorylase inhibitor presents a new treatment option for metastatic colorectal cancer patients refractory or intolerant to standard therapies
To collect more information about the usage and tolerability of FTD/TPI in clinical practice, we prospectively investigated the characteristics of patients with metastatic colorectal cancer (mCRC) refractory or intolerant to standard chemotherapies treated with FTD/TPI monotherapy within a compassionate use program (CUP), which was conducted from January 12 to August 14, 2016 in designated Colorectal cancer (CRC) centers in Germany and compared the rate and severity of adverse events (AE) to the data from the phase III trial RECOURSE

Summary

Introduction

Trifluridine/tipiracil (TAS-102, Lonsurf®), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine, FTD) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride, TPI) presents a new treatment option for metastatic colorectal cancer (mCRC) patients refractory or intolerant to standard therapies. The median overall survival (OS) from first-line therapy in metastatic disease has reached approximately 30 months [2,3,4,5,6,7,8]. FTD/TPI is an oral antimetabolite and has been shown to be effective in the treatment of patients refractory or intolerant to approved drugs for mCRC [14]. In addition FTD/TPI significantly prolonged median PFS; 2.0 vs 1.7 Months; HR 0.48; p < 0.0001), improved disease control rate ((DCR; 44.0% vs 16.3%; p < 0.0001) and prolonged median time to deterioration of ECOG performance status compared to placebo. The most overall common adverse events (AE) were leukopenia, neutropenia, anemia and thrombocytopenia and the most common AE ≥ grade 3 was neutropenia (38% of patients treated with FTD/TPI)

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