Pooled quality of life data reinforce the clinical outcomes obtained with trifluridine/tipiracil in patients with metastatic colorectal cancer
Trifluridine/tipiracil (FTD/TPI) is an established treatment for patients with recurrent metastatic colorectal cancer (mCRC). A pooled analysis of patient-reported quality of life (QoL) data from the two clinical trials forming the basis for this registration, confirm that the QoL and ECOG performance status are maintained in the majority of mCRC patients treated with this regimen. In addition to this, the analysis showed a significant association between the time to a deterioration of the ECOG PS and a change in the QLQ-C30 GHS score over time.
Based on the results of the PRECONNECT and TALLISUR trial, trifluridine/tipiracil (FTD/TPI) was approved for the treatment of mCRC patients who progressed on, or proved to be intolerable to standard therapies. While PRECONNECT was an international, multicenter, open-label, phase IIIb trial, TALLISUR was a prospective, multicenter, open-label phase IV trial. While both studies primarily focused on the efficacy and safety of FTD/TPI in this setting, quality of life (QoL) was an important secondary objective of both trials. During the 2022 World congress on gastrointestinal cancer, an analysis was presented pooling the patient reported QoL data from both these studies. In addition, the analysis assessed whether there was an association between QoL and changes in the Eastern Cooperative Oncology Group performance status (ECOG PS) of patients.
In both studies, patients with mCRC received FTD/TPI (35 mg/m2 twice-daily) on days 1–5 and 8–12 of each 28-day cycle, between 2016 and 2020. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (Version 3.0) questionnaire during each treatment cycle. The presented QLQ-C30 analysis included all patients who answered the questionnaire at baseline and at least once post baseline. A clinically relevant deterioration in QoL was defined as a drop of more than 10-points in the QLQ-C30 score from baseline or death. In addition to these questionnaires, the ECOG PS of patients was evaluated at baseline and during each cycle. In this respect, the study also recorded the time it took for the ECOG PS to deteriorate to ≥2.
In total, the FTD/TPI treated patient cohort consisted of 1100 patients: 914 treated in PRECONNECT and 186 enrolled in TALLISUR. As per protocol of both studies, the majority of patients had baseline ECOG PS score of 0 (N= 506), or 1 (N= 545). Two patients had an ECOG PS of 2 at baseline. For the population as a whole, the mean QLQ-C30 (global health score) score did not deviate from baseline by >10 points at any time point up to cycle 7. However, 450 patients did experience clinically meaningful deteriorations in their QLQ-C30 GHS at some point over the study period. The median time to this deterioration was 3.9 months. At the end of the study period, the ECOG PS was improved from baseline or maintained stable in about two thirds of patients (63.0%). Not surprisingly, a better ECOG PS at baseline was associated with a better QLQ-C30 GHS at baseline, with a mean QLQ-C30 GHS score at baseline of 67.8, 58.9 and 52.6 for patients with ECOG PS or 0, 1 and 2, respectively. Interestingly, a better ECOG PS at baseline also proved to be associated with a slower deterioration in the QLQ-C30 GHS, with a median time to deterioration of 4.2 months and 3.5 months for patients with an ECOG PS of 0 and 1, respectively. Patients in whom the ECOG PS improved from baseline did not display a deterioration in their QLQ-C30 GHS score (N= 45; mean change +0.74). In contrast, for patients in whose ECOG PS stayed unchanged (N= 544) or deteriorated (N= 340) a decrease in the QLQ-C30 GHS score was noted (mean change -2.84 and -8.88, respectively). In a Cox regression analysis, the association between time to ECOG PS deterioration and change in QLQ-C30 GHS score over time (change of ≥10 versus < 10) was significant (HR 1.707 [95% CI: 1.4, 2.2]; p < 0.0001).
Results of a pooled analysis of QoL data for patients treated with FTD/TPI in the PRECONNECT and TALLISUR trials, confirm that the QoL and ECOG PS were maintained in most patients. This is a particular clinical relevance given the palliative setting in which these patients are being treated. Furthermore, the analysis revealed a significant association between the time to a deterioration of the ECOG PS and a change in the QLQ-C30 GHS score over time.
Wyrwicz K, et al. Reinforcing clinical outcomes with patient-reported QoL outcomes in patients with mCRC receiving FTD/TPI: Pooled analysis of PRECONNECT and TALLISUR studies. Presented at ESMO GI 2022; Abstract SO-18