Real world aspects of palliative trifluridine plus tiperacil (TAS-102) in refractory metastatic colorectal cancer

Abstract

Background: While recent randomised phase III trials show that trifluridine/tiperacil (TAS-102) may prolong life in patients with refractory metastatic colorectal cancer (rmCRC), palliative aspects on its efficacy and tolerability in real world patients need further elucidation. Methods: A retrospective observational multicentre study was designed, including all patients with rmCRC who received TAS-102 under 2016-2019 in the South East Health Care region of Sweden. 48 patients were identified. Primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS), time to ECOG performance status deterioration (PSD), safety and dose reductions, admission to and duration of access to palliative care, and administration of TAS-102 in the last 30 days before death. Results: Median OS, PFS, and time to PSD (a proxy for impaired quality of life) from start of TAS-102 were 6.4 months (95% CI: 4.4-8.4), 2.3 months (95% CI: 1.8-2.7) and 2.5 months (95% CI: 1.9-3.2), respectively. Following uni-and multivariable regression analyses, the number of previous treatment lines (≤2 vs. ≥3) was statistically independent for OS (median 7.8 vs. 5.3 months, P=0.05), PFS (median 2.4 vs. 1.8 months, P=0.03), and time to PSD (median 2.8 vs. 1.8 months, P=0.03). Thirty-four (71%) of the patients received reduced doses. The most common grade 3-4 toxicity was neutropenia (39%). Forty-three (90%) were admitted to GP or hospital-based home palliative care. Median time for access to any form of palliative care before death was 2.3 (95% CI: 0.5-3.2) months. Few patients (n=3, 7%) received their last dose of TAS-102 in their last 30 days of life. Conclusions: The outcome and tolerability of TAS-102 in rmCRC appear similar in a real-world context and randomised trials. The retrospective design and limited sample size preclude firm conclusions on subgroup analyses, but it appears that the prognosis is slightly better the earlier TAS-102 is introduced. Treatment durations are generally short, and early admission to a palliative care provider is recommended.

Long Term Real-World Outcomes of Trifluridine/Tipiracil in Metastatic Colorectal Cancer—A Single UK Centre Experience

“…Median PFS was 2.8 months, an improvement on the results of RECOURSE. Other data available include published retrospective data, meta-analysis and abstracts [ 10 , 11 , 12 , 13 , 14 , 15 ]. Their reported outcomes are summarised in Table 1 .…”

Tas-102 for Refractory Metastatic Colorectal Cancer: A Multicenter Retrospective Cohort Study

“…The majority of patients (80%) included in our study received two or fewer previous lines of therapy. Similarly, in the Wallander et al [ 18 ] study, the subgroup of patients who had received two or fewer prior lines of treatment had a median OS of 7.8 months (CI 95%, 5.3–10.2), conversely patients who had received three or more lines had a median OS of 5.3 months (CI 95%, 3.1–7.5).…”

Case report: Long-term survival in a patient with metastatic colorectal cancer treated with trifluridine/tipiracil in the third-line setting

“…However, the improvements in median progression-free survival (PFS) in the presence of these factors was modest in the RECOURSE trial (5,11). Additional factors that may influence PFS or OS in patients treated with FTD/TPI include CEA <200 ng/ml, neutrophil-to-lymphocyte ratio <5, the development of grade 3 neutropenia, and the number of previous lines of therapy (12)(13)(14).…”