Background and importance Trifluridine-tipiracil (TAS102) is indicated in third- and/or fourth-line metastasic colorectal cancer (mCRC) after progression with standard treatments based on overall survival benefit shown in the RECOURSE and J003 studies. Longer survival is shown in patients who develop neutropenia as a toxicity.
Aim and objectives Analysis of correlation between efficacy of TAS102 and neutropenia.
Material and methods 43 patients with mCRC treated with this drug between January 2018 and September 2021 at Juan Ramón Jiménez Hospital (Huelva). Variables described: age, sex, KRAS mutation, performance status (PS), line of treatment and toxicities. Relationship between overal survival (OS) and progression-free survival (PFS) and the grade of neutropenia analysed by means of a Cox regression analysis, obtaining a hazard ratio. Survival medians presented using Kaplan–Meier curves.
Results Median age, 66 years. 58.3% were men. Only 6 patients with PS >2. 97.5% had neutropenia (51.3% grade 1, 41% grade 2 and 7.7% grade 3). All patients progressed, 79.1% have died to date.
The regression analysis was statistically significant (p=0.05); the variables grade of neutropenia and G3 neutropenia (neutrophils <1000–500/mm3 according to CTCAE) were significant for overall survival (p=0.009; HR 2.83; CI 1.35 to 5.9, p=0.028; HR 5.36; CI 1.199 to 23.985, respectively). There was also a correlation between PFS and neutropenia (p=0.004) but not with degrees of neutropenia.
The median OS in patients with neutropenia G2 was 1.8 months (CI 0.67 to 3.61) and 5.3 months for G3 neutropenia (CI 8.6 to 25.27). Median PFS for patients with neutropenia G2 was 2.6 months (CI 1.09 to 4.66) and 4.6 months for G3 neutropenia (CI 2.59 to 6.58).
Conclusion and relevance Neutropenia is a common adverse effect and the main dose-limiting toxicity. Data published in a Japanese series (Yohei Nose et al; Katsuya Makihara et al and T. Yoshino et al) have suggested a correlation between severity of neutropenia and survival. Similar outcomes were obtained in our study, with more favourable data mainly in OS in patients with grade 3 neutropenia. We understand neutropenia to be a possible efficacy predictor for TAS-102. More studies with a larger number of patients are necessary.
References and/or acknowledgements 1. Makihara K, Fukui R, Uchiyama H, et al. Decreased percentage of neutrophil is a prediction factor for the efficacy of TAS102 for pretreated metastatic colorectal cancer. J Gastrointest Oncol 2019;10(5):878–885.
Conflict of interest No conflict of interest
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.