Efficacy of trifluridine/tipiracil in 3rd or 4th line of treatment in patients with advanced or metastatic colorectal cancer: A real-world data analysis with subgroups exploration.
Authors: Hajac Lukasz , Tekiela Katarzyna , Malik Mateusz , Tosik Łukasz , Chowaniec Zbyszko , Kempa-Kaminska Natasza , Różycki Maciej , Barczyk Jakub , Hudziec Piotr , Sroka Anna , Migdał Monika , Marzec Ryszard , Sokołowski Marcin , Gabalewicz Katarzyna , Wisłocka-Rawson Lilianna , Hajac Martyna , Maciejczyk Adam , Cybulska-Stopa Bożena 
Published: June 2024

e15576

Background: Patients with unresectable mCRC can achieve long-term overall survival (OS) thanks to modern systemic treatment and subsequent lines of therapy. With effective 1st, 2nd and next lines of therapy, their condition often allows further lines of treatment. Since publication of RECOURSE study, one of the most frequently used drugs in the 3rd or 4th line is trifluridine/tipiracyl (FTD/TPI). There is limited data on optimal selection of patients in order to obtain the greatest therapeutic gain with the least toxicity. The aim of this study was to find and define groups of patients who would benefit most from this treatment in a real-world mCRC patient population. Methods: Consecutive patients with unresectable or metastatic colorectal cancer (mCRC) started treatment with FTD/TPI between 1/Sep/2019 and 31/Dec/2023. Clinical factors including age, gender, primary location of colorectal cancer, BRAF, RAS and MSI-H status, ECOG performance status, baseline CEA level, location of metastases, response to treatment and AEs occurrence were analyzed. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Jan/2024. Results: 822 medical records of patients with mCRC were analyzed. In total 261 patients treated with FTD/TPI were enrolled. 204 (78%) patients were treated with FTD/TPI in 3rd line (L3) and 57 (22%) in the 4th line (L4). Patients with RASmt were statistically more numerous in the L3 group; no other statistically significant differences in baseline characteristics was found between L3 and L4 groups. Estimated median OS (mOS) was 10.2 and 14.4 months in L3 and L4 group, respectively; no statistical significance was found between them (p = 0.0866; HR = 1.34, Cl 95% 0.9-1.9). Estimated median PFS (mPFS) was 7.4 and 4.6 months in L3 and L4 group, respectively, and statistically significant differences in mPFS was found in the L3 group in comparison to L4 (p = 0.0079; HR = 0.65, Cl 95% 0.5-0.9). Disease progression (PD) was found in 187 (92%) and 50 (88%) patients in the L3 and L4 group, respectively. PD was most common reason for discontinuing therapy. Most frequent serious AEs of grade 3 or higher were diarrhea, neutropenia and weakness. There were no grade 5 AEs and toxicity rarely led to discontinuation of FTD/TPI therapy. 102 (39%) patients were qualified for next line sequential systemic treatment after L3 or L4. Conclusions: Patients with mCRC who were treated with FTD/TPI in the 3rd line had better PFS than patients treated in 4th line, but mOS was statistically non-significantly better in L4 than L3, which requires further analysis. FTD/TPI is an effective therapy in subsequent lines of treatment for mCRC patients with acceptable toxicity.