Neutropenia as a predictor of efficacy in the treatment of metastatic colorectal cancer with TAS-102 (trifluridine - tipiracil).

Abstract

e15564 Background: TAS-102 (trifluridine - tipiracil) increases the survival of patients with metastatic colorectal cancer (mCRC) in 3rd or successive lines based on the results in overall survival (OS) of the phase 2 trial by Yoshino T et al and of the subsequent phase 3 RESOURCE and TERRA. It has a good toxicity profile, mainly at the gastrointestinal and hematological levels. Different publications relate neutropenia secondary to this drug with greater clinical benefit. Methods: Retrospective and multicenter observational study with patients diagnosed with mCRC treated with TAS-102 in the Juan Ramón Jiménez and General de Río Tinto hospitals (Huelva) between January 2016 and September 2021. We describe demographic data and other variables; subsequent Cox regression and multivariate analysis between OS and the different variables. We represent the OS median using Kaplan-Meier curves. Results: 47 patients were included. Median age 66 years; 66% men. No patient with ECOG > 2. Primary colon tumor in 55.4%; 72.3% with various metastatic locations. KRAS mutation in 63.8%. 78.8% in third line and the rest in fourth or successive. 80.9% have died. 82.9% abandoned due to progression and 8.5% due to toxicity: anemia 76.6% (grade ≥3 4.3%), neutropenia 74.5% (grade ≥3 44.7%), thrombocytopenia 10, 6% (grade ≥3 2.1%) and gastrointestinal 44.7% (grade ≥3 6.4%). The Kapplan Meier shows significant differences between the neutropenia curves 0 and grade 3-4 (median: 8 (95% CI 5.91-10.08) vs. 19 (95% CI 16.55-21.44) months; p = 0.043) and between the curves for grade 1-2 and grade 3-4 neutropenia (median: 8 (95% CI 2.9-13.09) vs. 19 (95% CI 16.55-21.44) months; p = 0.019). Cox regression identified grade 3-4 neutropenia and grade 1-2 anemia as positive predictors of OS. Multivariate analysis describes similar results (Table). Conclusions: Japanese series (Yohei Nose, et al; Katsuya Makihara, et al and T. Yoshino, et al) suggest a benefit in OS directly proportional to the degree of neutropenia found. In our study we obtain similar results, with better OS results for patients with grade 3-4 neutropenia. Therefore, we consider severe neutropenia as a possible predictor of the efficacy of TAS-102. Although our series is one of the largest published to date, we need more studies with a larger sample to obtain robust and enlightening results.[Table: see text]