A systematic review of observational studies of trifluridine/tipiracil (TAS-102) for metastatic colorectal cancer

<p><b>Background:</b> The treatment options for patients with therapy refractory metastatic colorectal cancer (mCRC) are sparse. TAS-102 (FTD/TPI) is a new oral anti-tumour agent composed of a nucleoside analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil, indicated for patients with mCRC who are refractory to standard therapies. This study summarizes published and unpublished experience with FTD/TPI in clinical practice settings.</p> <p><b>Patients and methods:</b> The Medline/PubMed, Embase and Cochrane Library databases were searched to identify observational studies on FTD/TPI monotherapy for mCRC. Papers describing use of FTD/TPI monotherapy outside clinical trials in series of patients evaluable for effectiveness were eligible. The outcomes of interest were median progression free survival (mPFS), median overall survival (mOS) as well as mean PFS time restricted to six months (PFS<sub>6m</sub>) and mean OS time restricted to one year (OS<sub>1y</sub>). Results of the pooled analyses of observational studies were compared to the results of the Japanese phase II trial and the two phase III trials, RECOURSE and TERRA.</p> <p><b>Results:</b> Seven published and two unpublished studies with 1008 patients from 64 centres were included for analysis. The pooled mPFS was 2.2 months (95% CI 2.1 to 2.3 months), and the pooled mOS was 6.6 months (95% CI 6.1 to 7.1 months). PFS<sub>6m</sub> was 2.9 months (95% CI 2.6 to 3.1 months) and OS<sub>1y</sub> was 6.8 (95% CI 6.0 to 7.5) months. While these results all reflect RECOURSE, the pooled mOS is lower than in the phase II trial and the OS<sub>1y</sub> is inferior to both the phase II trial and TERRA.</p> <p><b>Conclusion:</b> This systematic review and a meta-analysis indicates that in real life settings, the survival benefit of FTD/TPI monotherapy in patients with therapy refractory mCRC reflects the outcomes in RECOURSE but is inferior to outcomes in the two Asian efficacy trials.What is already known</p><p>TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC). A Japanese phase II trial and two phase III trials, RECOURSE and TERRA, demonstrated that FTD/TPI prolonged overall survival.</p>What this study adds<p>This systematic review and meta-analysis of real life data from 64 sites indicates that the effectiveness in daily clinical practice settings of FTD/TPI monotherapy in late stage mCRC reflects the outcomes in RECOURCE but is inferior to the outcomes in the Japanese phase II trial and TERRA.</p><p></p> <p>TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC). A Japanese phase II trial and two phase III trials, RECOURSE and TERRA, demonstrated that FTD/TPI prolonged overall survival.</p> <p>This systematic review and meta-analysis of real life data from 64 sites indicates that the effectiveness in daily clinical practice settings of FTD/TPI monotherapy in late stage mCRC reflects the outcomes in RECOURCE but is inferior to the outcomes in the Japanese phase II trial and TERRA.</p>