Factors Predicting Longer Survival in Patients with Metastatic Colorectal Cancer Treated with Trifluridine/Tipiracil
A recently published non-interventional analysis evaluated overall survival (OS) and progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) with favorable prognostic factors before initiating treatment with trifluridine/tipiracil compared to patients with unfavorable factors. It also identified which specific prognostic factors are favorable in terms of therapy effectiveness.
Previous Studies on Trifluridine/Tipiracil
The RECOURSE study in 2015 demonstrated the efficacy of an oral formulation containing the thymidine analog trifluridine and the thymidine phosphorylase inhibitor tipiracil in treating patients with refractory mCRC. Due to its survival benefits and low toxicity, trifluridine/tipiracil was approved for third-line treatment of mCRC regardless of the presence of RAS mutation. The cytotoxic effect of trifluridine, which is rapidly metabolized in the body, is preserved in this formulation thanks to tipiracil, which inhibits trifluridine's degradation and helps maintain its stable plasma concentration. Subsequent analysis of the RECOURSE study showed that low tumor burden and indolent disease are favorable prognostic factors associated with longer OS and PFS with trifluridine/tipiracil treatment.
Non-Interventional Registry Data Analysis
The cited study evaluated the impact of stratifying mCRC patients into groups with favorable and unfavorable prognostic factors on OS, PFS, and the safety of trifluridine/tipiracil treatment. The authors used data from an 18-month registry and conducted a retrospective observational study of patients who started trifluridine/tipiracil treatment from February 2018 to July 2019 at a single institution - the Portuguese Oncology Institute in Coimbra.
Patients had to have been previously treated with at least two lines of chemotherapy and had an ECOG performance status of 0-1. They were divided into a group with favorable prognostic characteristics (GPC: low tumor burden defined as < 3 metastatic sites and indolent disease defined as at least 18 months from the diagnosis of the first metastasis) and a group with unfavorable prognostic characteristics (PPC: high tumor burden and aggressive disease).
Evaluated Patient Population
Forty-nine patients were included, 22 (44.9%) with GPC and 27 (55.1%) with PPC. Among the GPC patients, 13 had liver metastases. The average age of the participants was 67 years (range 48-82 years), 67% were men, and 65% had metastases present at the initial CRC diagnosis. In the PPC group, patients more often had stage IV disease at CRC diagnosis, had undergone ≥ 4 previous lines of treatment, and more often had RAS mutations. Other characteristics of the two groups were comparable.
Results
The median OS in the entire population was 7.5 months. In the GPC group, it was significantly longer (11.4 months) compared to the PPC group (3.9 months; p < 0.0001). The median OS improvement in GPC patients was independent of the presence of RAS mutations, patient age, and performance status. Another favorable prognostic factor identified in this group was the absence of liver metastases. GPC patients without liver metastases had an OS of 16.7 months compared to 8.3 months for GPC patients with liver metastases (p = 0.019).
Similarly, the median PFS was significantly longer in the GPC group than in the PPC group (4.9 vs. 2.6 months; p < 0.0001). Absence of liver metastases was also a favorable prognostic factor for this parameter – associated with a PFS of 6.4 months compared to 3.7 months for GPC patients with liver metastases (p < 0.0001).
Conclusion
The study confirmed greater efficacy of trifluridine/tipiracil in GPC patients compared to PPC patients while maintaining a well-tolerated safety profile. Favorable prognostic factors influencing the sustained response to trifluridine/tipiracil were identified as indolent disease, low tumor burden, and absence of liver metastases.
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Abridged information about Lonsurf can be found HERE.
Sources:
1. Sousa M. J., Gomes I., Pereira T. C. et al. The effect of prognostic factors at baseline on the efficacy of trifluridine/tipiracil in patients with metastatic colorectal cancer: a Portuguese exploratory analysis. Cancer Treat Res Commun 2022; 31: 100531, doi: 10.1016/j.ctarc.2022.100531.
2. SPC Lonsurf. Available at: www.ema.europa.eu/en/documents/product-information/lonsurf-epar-product-information_cs.pdf
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