Effectiveness and safety of trifluridine/tipiracil in patients with metastatic colorectal cancer in clinical practice in Poland

Trifluridine/tipiracil is indicated for adult patients with metastatic colorectal cancer (mCRC) previously treated (refractory), or not considered as candidates for available therapies. The randomized phase 3 RECOURSE trial showed a significant increase in median overall survival (OS) of 1.8 months compared to the placebo, significant benefit in progression-free survival (PFS), and prolonged time to ECOG PS worsening. We assessed the effectiveness and safety of trifluridine/tipiracil in daily clinical practice before public reimbursement in Poland. We collected data from patients treated with trifluridine/tipiracil at eleven polish oncology centers according to approved indications. In this retrospective patient cohort, trifluridine/tipiracil was donated to the hospitals or was bought out-of-pocket by patients. Baseline characteristics of patients, safety, and survival times were assessed. Baseline characteristics were tested in uni- and multivariate analyses for prognostic significance of PFS and OS. A total of 123 patients with a median age of 60 years, treated from Feb. 2017 to Dec. 2019 were analyzed. Fifty-eight patients (47%) did not meet the RECOURSE trial eligibility criteria with having administered prior antiangiogenic treatment (41%) and/or being in ECOG PS 2 (7.3%). Four (3.2%) and 44 (36%) patients achieved response and disease stabilization, respectively. The median PFS was 3.2 months and the primary tumor location, KRAS-mutation status, site of metastases, BMI, ECOG PS, and Platelet-to-Lymphocyte Ratio were prognostic factors for PFS. The 6-month PFS rate was 24% and the primary tumor location in the left side colon, WT KRAS status, WT BRAF status, more than 3 lines of previous treatment, ECOG PS 0 and Platelet-to-Lymphocyte Ratio ≥130 were independently associated with higher chances of a patient being progression-free at 6 months. The most common grade ≥3 toxicities were neutropenia (35%), leukopenia (9.6%), anemia (12%), fatigue (9,6%) and diarrhea (3,2%). Our data show that treatment with trifluridine/tipiracil in daily clinical practice is feasible and safe. Forty-eight patients (39%) achieved clinical benefit with trifluridine/tipiracil. Patient characteristics such as left side primary tumor location, WT KRAS status, WT BRAF status, more than 3 lines of previous treatment, ECOG PS 0 and Platelet-to-Lymphocyte Ratio ≥130 may be helpful to identify 6 month progression-free survivors.