TAS 102 in refractory metastatic colorectal cancer: UK Expanded Access Programme experience.

Abstract

e15043 Background: Trifluridine/tipiracil (TAS-102), an oral combination of a nucleoside analogue and thymidine phosphorylase inhibitor, showed significant survival benefit in the RECOURSE study. We assessed TAS-102 clinical activity in an unselected patient population with refractory metastatic colorectal cancer in the UK Expanded Access Programme (EAP). Methods: Pharmacy databases were used to identify patients treated with TAS-102 on the UK EAP at three tertiary referral Cancer Centres (Manchester, Cardiff and Southampton) between December 2015 and December 2016. Case notes, laboratory tests and histopathology were reviewed to ascertain survival data and prognostic variables. Results: Of the 78 patients treated with TAS-102, median ECOG PS was 1, 56% of patients were male and median age was 64 years (range 27- 80 years). 31 patients had 3 or more metastatic sites of disease. 26 patients were RAS mutant and 1 patient was B-RAFmutant. Median number of cycles of TAS-102 was 2 cycles (range 1-11 cycles) with one third of patients requiring a dose reduction due to toxicity. 39% of patients developed grade 3 or 4 neutropenia and 12% febrile neutropenia. Response assessment was not performed in 12 patients due to death prior to assessment (6 patients) or withdrawal of patient consent for TAS-102 treatment (6 patients). Where best disease response was assessed by RECIST 1.1 criteria, 26.6% patient showed clinical benefit (stable disease or partial response) whereas 73.3% of patients had confirmed progressive disease. Median follow-up period was 5.2 months with 45 deaths in the study period. Median overall survival (OS) was 6.6 months. OS was significantly worse for patients with hypoalbuminemia (Albumin < 30g/dl) at cycle 1 day 1 TAS-102 (p = 0.028). Anaemia, renal or liver impairment and number of metastatic sites of disease had no impact on patient survival. RAS mutant colorectal cancer patients showed a trend to improved outcome on TAS-102 which did not reach statistical significance within the study follow-up period. Conclusions: TAS-102 shows modest clinical benefit in treatment refractory metastatic colorectal cancer patients on the UK expanded access programme.