engleski

A multicenter exploratory analysis of the possible predictive factors for trifluridine/tipiracil in refractory metastatic colorectal cancer

Background: Trifluridine/tipiracil (TTP) is an orally administered cytotoxic agent approved for treatment of patients with metastatic colorectal cancer (mCRC) after progression to at least two prior regimens of standard therapy with survival benefit demonstrated in two phase 3 trials. TTP is accepted as a standard third- or fourth-line treatment option following progression to at least two prior regimens of standard therapy. Patients with low tumor burden, indolent disease and without liver metastases seem to derive greater survival benefit as demonstrated in the exploratory analysis of the RECOURSE trial. However, reports based on the real-world data on which patients will benefit the most are scarce, especially on the multicenter level. Methods: We conducted a retrospective exploratory study on the effectiveness of TTP in mCRC patients. The TTP was administered in the 3rd and 4th line after progression on two standard lines of treatment consisting of fluoropyrimidines, oxaliplatin, irinotecan, and anti-VEGF or anti-EGFR therapy. We included 212 patients who received TTP from three Croatian university hospitals: University Hospital Centre Zagreb (Zagreb), University Hospital Split (Split), and Sestre milosrdnice University Hospital Center (Zagreb). Outcomes, measured as PFS and OS, were estimated using the Kaplan-Meier method and curves were compared using the log-rank test. Patients lost to follow-up were censored at their last hospital visit. Cox regression analysis was used to examine the association between survival, age, location of the primary tumor, ECOG performance status, RAS status, previous biological therapy, cumulative duration of treatment in the first and second line (standard treatment, ST), tumor burden and liver metastases. Data on PFS and OS were censored at 12- and 18- months cutoff, respectively. Results: The median age was 64 years and the median duration of ST was 19.55 months. We divided the patients into two groups in regard to the duration of ST. Patients with ST < 18 months (n¼91, group A) were considered to have a more aggressive disease as opposed to 18 months (n¼121, group B) indicating an indolent disease. Median PFS for group A and B was 2.40 (95%CI 1.907-2.893) and 2.57 months (95%CI 2.341-2.799), respectively, with p¼0.152. OS was also in favor of group B with median 6.27 (95%CI 5.253-7.287) vs 5.73 months (95%CI 4.975- 6.485) in group A (p¼0.189). Although there was a numerical advantage in patients with less aggressive disease, in both cases statistical significance was not achieved. Cox regression analysis revealed longer PFS and OS in older patients and in those of better general condition (ECOG 0). There was no influence on survival from other covariates. Conclusions: Although lacking statistical significance, our results support that patients with more indolent clinical course of the disease tend to derive somewhat greater survival benefit from trifluridine/tipiracil. Furthermore, the greatest benefit was demonstrated in older patients and with best performance status regardless of tumor characteristics or previous therapy.

exploratory analysis ; predictive factors ; trifluridine/tipiracil ; refractory colorectal cancer

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