Prognostic stratification of TAS-102 treatment

In metastatic colorectal cancer (mCRC) the choice of treatment should take into account the characteristics of the tumor and the patient, as well as its efficacy and tolerability. The RECOURSE study demonstrated that the presence of low tumor burden and indolent disease has an impact on progression-free (PFS) and overall (OS) survival of patients treated with trifluridine/tipiracil (TAS-102).

Retrospective study that included mCRC patients undergoing TAS-102 from January 2017 to December 2021. The analysis was performed considering two subgroups: good prognosis (GP) - (1 or 2 metastasis sites and time ≥ 18 months since metastasis diagnosis to initiation of TAS-102) and poor prognosis (PP) - (≥ 3 metastasized sites and/or time < 18 months since metastasis diagnosis to TAS-102 initiation). Survival analysis was performed using the Kaplan-Meier method and the log-rank test. The prognostic impact was assessed using the Cox regression model.

A total of 85 patients were included, 51.8% (n=44) male, with a median age of 65 years [24-85]. About 58.8% (n=50) were metastasized at diagnosis and 61.2% had a mutation in the RAS gene. About 80% (n=68) had an ECOG performance status of 0-1, 45.9% (n=39) had ≥ 3 metastatic sites and 72.9% (n=62) had liver metastases. In the total sample, 48.2% (n=41) had characteristics of GP and 51.8% (n=44) of PP. In 84.7% (n=72) of patients, TAS-102 was performed in the 3rd or 4th line of treatment. Median follow-up was 3 months (1-18). There was a statistically significant impact on OS and PFS of patients treated with TAS-102 taking into account the two prognostic subgroups (median PFS GP 5 months, 95%CI 4.1-5.9 versus PP 3 months, 95%CI 2.5-3.6, p=0.001; median OS GP 13 months, 95%CI 7.4-18.6 versus PP 5 months, 95%CI 4.3-5.7, p < 0.001). In the multivariate analysis, the presence of GP features was identified as an independent prognostic factor with an impact on PFS (HR 0.52, 95%CI 0.3-0.9, p=0.017) and OS (HR 0.47, 95%CI 0.3-0.8, p=0.004). Mutated RAS tumors were associated to a worse prognosis (HR 1.7, 95%CI 1.7-2.8, p=0.035).

In our analysis, greater efficacy of TAS-102 was observed in the presence of GHP features in mCRC. Taking into account the advanced stage of the disease, the patient's vulnerability and socio-economic impact, the selection of patients who benefit from this therapy becomes increasingly relevant in an attempt to avoid therapeutic obstinacy and the underlying iatrogenesis.

The authors.

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All authors have declared no conflicts of interest.