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

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.

Review of metastatic colorectal cancer treatment pathways and early clinical experience of trifluridine/tipiracil in the UK named patient programme

“…The reasons for these differences are unclear but may reflect differing clinical practice in the evaluation and recording of ECOG-PS scores in different countries, or may suggest that patients included in the German and UK NPPs were at a more advanced stage of disease at enrolment. The number and type of previous treatments observed were similar to those reported in observational studies from the Netherlands [14], Japan [15], Latvia [16] and Germany [17]. However, a smaller proportion of the patients receiving trifluridine/tipiracil in this analysis had at least 4 prior treatment regimens (19%) than in the RE-COURSE trial [10] (60%).…”

“…However, there was a higher proportion of patients in the RECOURSE trial [10] and the Italian single-centre compassionate use programme (CUP) [13] with ECOG-PS scores of 0 (56 and 63% respectively) than patients enrolled in the UK NPP (28% of patients receiving ≥1 dose of trifluridine/tipiracil, 14% of patients not receiving trifluridine/tipiracil). The patients enrolled in the UK NPP were more similar to the sample reported in the German CUP, in which 28% of patients had ECOG scores of 0 [17]. The reasons for these differences are unclear but may reflect differing clinical practice in the evaluation and recording of ECOG-PS scores in different countries, or may suggest that patients included in the German and UK NPPs were at a more advanced stage of disease at enrolment.…”

“…Patients receiving trifluridine/tipiracil in the UK NPP received a median of 2 (range 1-20) cycles of trifluridine/ tipiracil (similar to the German CUP [17]), and had a median treatment persistence of 1.8 (95% CI 1.8-2.4) months, which is broadly similar to the RECOURSE trial population (5.7 weeks) and slightly shorter than reported for the Italian single centre CUP (2.8 months) [10,13]. The primary reason for treatment discontinuation was disease progression (79%), similar to that reported in United States (USA) expanded access programme (EAP) [23], the Italian (single centre) and Latvian compassionate use programmes [13,16].…”

“…Subsequent post-hoc analysis of RECOURSE trial data has demonstrated the clinical efficacy and tolerability of trifluridine/tipiracil in various subgroups [11] and clinically meaningful improvements in quality-adjusted survival [12]. There is further evidence supporting the clinical effectiveness and tolerability of trifluridine/tipiracil in various geographies [13][14][15][16][17][18].…”

Metastatic Colorectal Carcinoma after Second Progression and the Role of Trifluridine-Tipiracil (TAS-102) in Switzerland

“…Several compassionate use programs of FTD/TPI across Europe, the USA, and Asia have been conducted and in summary they underline the efficacy and safety of FTD/TPI in a real-world population with refractory mCRC [17][18][19][20][21].…”