Real-World Data of Patients with V600E-Mutated Metastatic Colorectal Cancer Treated with Trifluridine/Tipiracil.

Background: For patients with refractory metastatic colorectal cancer (mCRC), trifluridine/tipiracil (FTD-TPI) has been associated with a significant improvement in overall survival (OS). However, data are lacking regarding the activity of FTD-TPI in patients with -mutated mCRC.

Methods: This retrospective, multicenter, international cohort included patients with -mutated mCRC treated with FTD-TPI in a real-life setting in Spain and Italy. Survival analysis was performed using Kaplan-Meier methods and Cox proportional hazard models and according to established prognostic groups: good prognosis characteristics (GPC; < 3 metastatic sites and time from metastases to FTD-TPI ≥ 18 months) and poor prognosis characteristics (PPC; ≥ 3 metastatic sites or time from metastases to FTD-TPI < 18 months).

Results: In the 26 patients included, the median age was 61 years, 13 (50%) were female, and 20 (77%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Fourteen (56%) patients had right-sided tumors, six (23%) had microsatellite instability tumors, and thirteen (50%) had liver metastases. Median progression-free survival was 2.3 months (95% CI 2.0-3.2), and median OS (mOS) was 6.6 months (95% CI 4.4-12.0). mOS was 7.6 vs. 4.2 months (HR 1.64, 95% CI 0.65-4.10, = 0.3) for GPC and PPC patients, respectively. Exploratory analyses identified ECOG as the only feature associated with survival. The most frequent grade 3-4 adverse events were neutropenia (8%), anemia (8%), and asthenia (4%).

Conclusions: Patients with mutant mCRC achieved modest benefits with FTD-TPI; however, patients with GPC and ECOG 0 achieved longer OS compared with those with PPC or ECOG 1-2, thus warranting further exploration in prospective cohorts.