Retrospective analysis of clinical factors associated with a greater benefit with Trifluridine and Tipiracil in metastasic colorectal cancer
Authors: N. Rodriguez-Salas, M. Soriano Segura, A. Jimenez-Gordo, R. Molina, J. Cámara, A. Lopez Alfonso, B. Martínez-Amores, A. Pertejo Fernandez, G. Reynoso, J. Miranda Poma
Journal: Annals of Oncology (2018)

Introduction: Colorectal cancer (CRC) is the most incident in Spain, according to Spanish Network of Cancer Registries (REDECAN) and is the second cause of death by cancer in Spain. Although the OS in metastatic setting has increased to 24-30 months, the 5-year OS continues to be less than 12%. The first and second line of treatment are well defined; however, there are few therapeutic options for those patients who have progressed to these standard therapies. After progression to the second line of treatment, the only therapeutic options with approved specific indication are Regorafenib and Trifluridine and Tipiracil. Trifluridine and Tipiracil has shown its efficacy in two randomized clinical trials comparing Trifluridine and Tipiracil versus placebo: a Phase II and a Phase III study (RECOURSE). In the previous Phase II study, the mOS was 9.0 months in the group treated with Trifluridine and Tipiracil, compared to 6.6 months in the placebo group. In the RECOURSE study, among patients treated with Trifluridine and Tipiracil mPFS was 2 months versus 1.7 months among those treated with placebo, and mOS was 10,5 with Trifluridine and Tipiracil vs 7,6 with placebo. We described the clinical characteristic of patients treated with Trifluridine and Tipiracil in seven hospitals from Madrid; identifying and analyzing clinical factors associated with long-term response. Methods: We collected retrospectively the clinical data of 98 patients who had received treatment with Trifluridine and Tipiracil until January 2018 in seven different hospitals in Madrid. Results: The mean age at first use of Trifluridine and Tipiracil was 66± 9.45 years, 57.5% were men and 42.3% were women, most of them in good performance status (ECOG 0-1: 71.2%), 27.8% had ECOG ≥2 when started Trifluridine and Tipiracil. All of the patients were diagnosed of metastatic colorectal cancer (73.2% had liver metastases, 58.2% lung metastases and 30.9% peritoneal metastases). Tumor localization was: 73.2% left colon, 24.8% right colon, and only 2% small intestine or 1% two synchronous colonic tumors. KRAS mutations were found in 62.9%, NRAS mutations in 17.4% and BRAF mutations were found in 5.4% patients. The median of prior lines of chemotherapy was three. The median progression free survival was 3 months (95% CI 2.65 – 3.36). The median overall survival was 5 months (95% CI 4.23-5.78). The median duration of treatment was 3 cycles. 23.7% patients had an adverse event that led to treatment withdrawal. The requirement of dose-reduction was associated with longer PFS (4 months vs 3 months, p = 0.002) and OS (14 months vs 5 months, p = 0.017). The existence of BRAF mutation was also associated with shorter PFS (1 month vs 3 months, p = 0.002) and OS (1 month vs 5 months, p = 0.000). There was no statistically significant difference of PFS and OS according to primary tumor location. Conclusion: Trifluridine and Tipiracil is effective in metastatic colorectal cancer (in patients with ≥2 lines of treatment). The OS (5 months) and PFS (3 months) reached in our study in real clinical practice are consistent with findings from previous studies. Mutational status of BRAF was statistically significant associated with shortened PFS and OS. Dose reduction during treatment is associated with Trifluridine and Tipiracil efficacy in terms of prolonged OS and PFS.