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RETRO-TAS, a retrospective observational study of rifluridine/tipiracil in chemorefractory metastatic colorectal cancer
Background
Trifluridine/tipiracil (TAS-102) is an oral combination of an antineoplastic thymidine-based nucleoside analogue, trifluridine, and the thymidine phosphorylase (TPase) inhibitor, tipiracil hydrochloride, indicated for patients (pts) with metastatic colorectal cancer (mCRC) as third line therapy. The approved dose of TAS-102 in adults is 35 mg/m2/dose administered orally twice daily on Days 1 to 5 and Days 8 to 12 of each 28-day cycle as long as benefit is observed or until unacceptable toxicity occurs. We conducted an investigator initiated retrospective analysis in patients with chemorefractory mCRC treated with TAS-102 to record clinical practice and to collect real world data on the clinical efficacy of TAS-102 in the Greek population.
Methods
Clinicopathologic characteristics of patients treated in 8 Cancer Centres were collected to assess physician's choice of treatment in chemoresistant mCRC with TAS-102 in third line and beyond. In addition, the clinicopathologic features related to mCRC (focus on molecular profile), duration of treatment, dose modification and toxicity were analysed. The PFS, the OS, the 6-/8-month PFS rate and the disease control rate were calculated. Prognostic factors were evaluated by Cox regression model and Kaplan-Meier curves, along with log-rank tests using Stata/MP 16.0 for Windows.
Results
From October 2018 to October 2021, 200 patients with a median age at diagnosis of 63.7 years (IQR 54.2, 72.1) and at TAS-102 treatment initiation was 67.0 (IQR 58.0, 75.0). At the time of the analysis the median follow-up time was 14 months (IQR 7, 23), 158 PDs and 106 deaths were recorded. Of all patients 42% were females and 58% were metastatic at diagnosis. Molecular analysis revealed mutations in KRAS (52%), NRAS (5%), HER2 (3.5%), BRAF (3.5%) and MSI (9%). Adjuvant chemotherapy and radical surgery was delivered in 39.5% and 51.5% respectively. TAS-102 was administered as a third (70.5%), fourth (17.0%) or fifth line (12.5%) of therapy. Serious adverse events reported were neutropenia (4pts), anemia (2pts), thrombocytopenia (1pt), diarrhea (1pt), nausea (1 pt) and fatigue (8 pts). Dose reduction, delay of initiation of the next cycle and shorter duration of therapy was reported in 25%, 31% and 14.5% of patients. Patients received TAS-102 as monotherapy (71.5%), in combination with bevacizumab (24.5%) or with an anti-EGFR agent (4.0%). The median duration of TAS-102 therapy was 119.5 days and 81% of patients discontinued therapy due to progressive disease. Objective responses during TAS-102 therapy included 0.5% CR, 25% PR, 20% SD and 47% PD, while 7.5% of patients were not evaluable. The median PFS time was 4.8 and the median OS was 11.4 months. The 6 and the 8-month PFS rate was 41.4% and 31.5% respectively. In the multivariable analysis PS>1 and metastatic disease in the liver and lung were adversely associated with survival whereas tumor sidedness and mutational status were not.
Conclusions
This real-world observational study confirms and adds on the findings of the RECOURSE phase III study in relation to the toxicity and the effectiveness of TAS-102 in all subgroups of patients with chemotherapy refractory mCRC, regardless of mutational status and sidedness.
Clinical trial identification
RETRO-TAS study NCT04965870.
Legal entity responsible for the study
The authors.
Funding
Hellenic Study Group of Psychoneuroimmunology in Cancer.
Disclosures
J. Souglakos: Honoraria (Institution): Servier; Advisory / Consultancy: Servier; Travel / Accommodation / Expenses: Servier. All other authors have declared no conflicts of interest.
