Survival benefit and maintained quality of life with trifluridine/tipiracil-bevacizumab in refractory metastatic colorectal cancer
Previously, the phase III SUNLIGHT study showed that the combination of trifluridine/tipiracil (FTD/TPI) with bevacizumab (bev) was associated with a significantly better progression-free (PFS) and overall survival (OS) than FTD/TPI alone in patients with refractory metastatic colorectal cancer. During ESMO World GI 2023, quality of life data of this trial show that this benefit is accompanied by a maintained quality of life, with a trend for a longer time to a deterioration in health-related quality of life (HRQoL) with FTD/TPI + bev than with FTD/TPI alone.
Background
The SUNLIGHT trial is a phase III study comparing the efficacy and safety of FTD/TPI plus bev to FTD/TPI monotherapy in patients with refractory metastatic colorectal cancer (mCRC). Previously, results of this trial showed that the addition of bevacizumab to FTD/TPI results in a 3.3-month improvement in the median OS compared to FTD/TPI alone (10.8 vs. 7.5 months; HR: 0.61; p< 0.001). In addition, also the median PFS was 3.2 months longer with the FTD/TPI + bev combination than with FTD/TPI alone (5.6 vs. 2.4 months; HR: 0.44; p< 0.001). During the 2023 World congress on gastro-intestinal cancer, health-related quality of life (HRQoL) data of this trial were presented.
Study design
The SUNLIGHT study randomized 492 patients with histologically confirmed mCRC who had disease progression after 2 lines of therapy to receive either FTD/TPI (35 mg/m2 PO twice daily on days 1–5 and 8–12 of a 28-day cycle) (N= 246) or the same dose of FTD/TPI in combination with bev (5 mg/kg on day 1and day 15) (N= 246). OS was the primary endpoint of this trial, with PFS, safety, the time to a deterioration in ECOG performance status and QoL as secondary objectives. HRQoL was evaluated at baseline, at each cycle, and at withdrawal using the EORTC QLQ-C30 and EQ-5D-5L questionnaires. QoL outcomes were defined as the mean change from baseline in QLQ-C30 domains (at least 10 points were considered as the minimal important difference) and as the time to a deterioration.
Results
Of the 492 patients randomized in the study, 239 and 241 (>97%) had QoL data at baseline in the combination and monotherapy arms, respectively. For both questionnaires, the mean baseline scores were similar throughout the treatment and showed a comparable HRQoL score without any clinically relevant changes over time. Patients treated with FTD/TPI + bev or with FTD/TPI monotherapy, did not experience an increased symptom burden as assessed by the QLQ-C30 symptom domains. Patients receiving FTD/TPI plus bev had a reduced risk for a definitive worsening in the global health status (GHS) of more than 10 points compared to patients receiving FTD/TPI alone (median: 8.54 vs. 4.7 months; HR[96%CI]: 0.50[0.38-0.65]). In a further sensitivity analysis, the HRQoL deteriorated significantly later with the combination of FTD/TPI + bev than with FTD/TPI alone (median GHS: 4.5 vs. 2.07 months; HR[95%CI]: 0.49[0.40-0.60]). A similar result was observed with the EQ-5D-5L utility score and VAS showing that patients treated with the combination were less likely to deteriorate earlier than patients treated with FTD/TPI monotherapy.
Conclusions
The HRQoL was maintained in both arms of the SUNLIGHT study, with a trend for a prolonged time to a definitive deterioration in HRQoL with FTD/TPI + bev compared to FTD/TPI alone.
Reference
Prager G., et al. Health-related quality of life associated with trifluridine/tipiracil in combination with bevacizumab in refractory metastatic colorectal cancer: an analysis of the phase III SUNLIGHT trial. Presented at ESMO World GI 2023; Abstract O-9.
