O-9 Health-related quality of life associated with trifluridine/tipiracil in combination with bevacizumab in refractory metastatic colorectal cancer: An analysis of the phase 3 SUNLIGHT trial

The SUNLIGHT trial, an international, open-label, randomised, phase 3 study comparing trifluridine/tipiracil (FTD/TPI) plus bevacizumab (bev) to FTD/TPI monotherapy in patients with refractory metastatic colorectal cancer (mCRC), demonstrated that the combination of FTD/TPI + bev significantly improved overall survival (OS) and progression-free survival (PFS) with a predictable and manageable safety profile. The median OS was improved by 3.3 months with FTD/TPI + bev (10.8 months with FTD/TPI + bev vs. 7.5 months with FTD/TPI), hazard ratio of 0.61 (95% CI, 0.49 to 0.77; P < 0.001). Median PFS in the FTD/TPI + bev group was of 5.6 months vs. 2.4 months in the FTD/TPI group (hazard ratio, 0.44; 95% CI, 0.36 to 0.54; P < 0.001). Here, we report health-related quality of Life (HRQoL) outcomes. HRQoL was evaluated at baseline, at each cycle, and at withdrawal visit using EORTC QLQ-C30 and EQ-5D-5L questionnaires. QoL outcomes were defined as mean changes from baseline in QLQ-C30 domains (at least 10 points were considered as the minimal important difference) and time to deterioration. Post-hoc analyses assessing the time to definitive worsening of EQ-5D-5L utility score and visual analog scale (VAS) by more than 0.08 and 7 points respectively, are reported. Among the 492 randomized patients, 239 and 241 (>97%) had QoL data at baseline in the combination and monotherapy arms, respectively. The cut-off point for the analysis was 12 cycles for FTD/TPI + bev and 6 cycles for FTD/TPI monotherapy owing that higher number of cycles were associated with a lower completion rate ( < 10%) not allowing us a meaningful interpretation. For both questionnaires, mean baseline scores were similar throughout the treatment and showed a comparable HRQoL scores with no clinically relevant changes over time. Patients treated with FTD/TPI + bev or with FTD/TPI monotherapy, did not show increased symptom burden as assessed by the QLQ-C30 symptom domains. Patients receiving FTD/TPI plus bevacizumab had a reduced risk of global health status (GHS) definitive worsening of more than 10 points (median time to worsening in GHS was 8.54 months in the FTD/TPI + bev arm vs. 4.7 months in the FTD/TPI arm [hazard ratio, 0.50; 95% CI, 0.38 to 0.65]) and in all scales and subscales. In a sensitivity analysis considering disease progression and death as a definitive deterioration measured by QLQ-C30, HRQoL deteriorated significantly later (median GHS in the FTD/TPI + bev group was of 4.5 months vs. 2.07 months in the FTD/TPI group (hazard ratio, 0.49; 95% CI, 0.40 to 0.60), consistently favoring the combination arm. 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 before those treated with FTD/TPI monotherapy. QoL was maintained in both arms with a trend toward a prolonged time to definitive deterioration of HRQoL scales and subscales in FTD/TPI + bev as compared to FTD/TPI monotherapy.