Clinical outcome of patients with chemorefractory metastatic colorectal cancer treated with trifluridine/tipiracil (TAS-102): a single Italian institution compassionate use programme

Abstract

BackgroundTAS-102 improves overall survival (OS) in patients with metastatic colorectal cancer (mCRC) refractory to standard treatments. However, predictive biomarkers of efficacy are currently lacking.Patients and methodsWe treated a cohort of 43 chemorefractory mCRC patients treated with TAS-102, in a single institution expanded access, compassionate use programme. We stratified patients in two groups according to number of cycles received (<6 cycles and ≥6 cycles). OS, progression-free survival (PFS) and safety were evaluated.ResultsThirteen out of 43 patients (30%) obtained a clinically relevant disease control with TAS-102 therapy. Eleven of them were treated for ≥6 cycles with TAS-102, reaching a median PFS of 7.5 months (95% CI 5.8 to 9.2 months) and a median OS of 11.2 months (95% CI range not reached yet). A trend towards significance (p=0.08) between a good performance status and response to TAS-102 was observed. Further, 7 out of the 11 TAS-102 long-treated patients achieved a clinical benefit from a previous treatment with regorafenib. A significant correlation between regorafenib and TAS-102 clinical efficacy was observed (p=0.008). Six out 13 regorafenib-naïve patients were treated with regorafenib after progression from TAS-102. All these patients achieved SD with a median duration of treatment with regorafenib of 6.1 months (range, 1.6–6.7).ConclusionPatients with mCRC in good clinical conditions, even though having been heavily pretreated with all the available treatment options, could obtain a significant clinical benefit from treatment with TAS-102. Moreover, a previous clinical benefit obtained with regorafenib is potentially predictive of clinical efficacy of subsequent TAS-102 treatment.

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

“…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]. Date of death was not available for most patients in the UK NPP precluding analysis of progression-free survival; however, in patients discontinuing due to disease progression, median progression-free duration was 2.8 (95% CI: 2.4-2.9) months.…”

“…The demographics and clinical characteristics of patients enrolled in the NPP who went on to receive at least one dose of trifluridine/ tipiracil were broadly similar to those not receiving trifluridine/tipiracil. Furthermore, patients enrolled had similar demographic characteristics (median age, sex) to those in the RECOURSE trial [10] and several real-world studies [13][14][15][16]. 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).…”

“…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].…”

Real‐world treatment patterns and outcomes in refractory metastatic colorectal cancer

“…Maximizing the exposure of active agents has been the cornerstone strategy to improving mCRC patient outcomes . Previous registration trials have confirmed the benefit of treatment in the refractory setting, such that regorafenib or TAS‐102 can benefit patients who received ≥ 3 lines of therapy, and a substantial proportion of patients can have disease control with TAS‐102 after regorafenib exposure . In the current study, patients who received post‐3L therapy had better OS than those who stopped after 3L treatment (15.1 vs 6.0 months, HR = 0.41, P = 0.002).…”

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

“…For this reason the number of patients in the German CUP, which were pretreated with regorafenib, is significantly lower than in patients of other European CUPs published recently. For example 70% of patients in the Italian CUP were pretreated with regorafenib compared to only 33.6% in the here reported patient population [20]. In addition, in Germany patients with advanced CRC are not only treated in large academic centers but also in smaller hospitals or private practices.…”