Effect of trifluridine/tipiracil in combination with bevacizumab on ECOG-PS in refractory metastatic colorectal cancer: An analysis of the phase 3 SUNLIGHT trial.
Authors: Taieb Julien , Prager Gerald W. , Fakih Marwan , Ciardello Fortunato , Van Cutsem Eric , Elez Elena , Cruz Felipe Melo , Wyrwicz Lucjan , Stroyakovskiy Daniil , Papai Zsuzsanna , Poureau Pierre-Guillaume , Liposits Gabor , Cremolini Chiara , Bondarenko Igor , Modest Dominik Paul , Amellal Nadia , Hassan Hasnaa , Skanji Donia , Tabernero Josep 
Published: June 2023

3594 Background: SUNLIGHT, an international, open-label, randomized, phase 3 study comparing trifluridine/tipiracil (FTD/TPI) in combination with bevacizumab versus FTD/TPI monotherapy in patients with metastatic colorectal cancer (mCRC) met its primary endpoint (overall survival [OS]) and key secondary endpoint (progression free survival [PFS]). Primary and key secondary outcomes in patients with maintained ECOG-PS are reported. Methods: SUNLIGHT enrolled patients with ECOG-PS 0/1. ECOG-PS was evaluated at baseline, at each treatment cycle, and at withdrawal visit. Worst ECOG values and time to ECOG worsening of more than 2 were reported. Here we report a post-hoc analysis assessing OS and PFS in patients who remained at ECOG-PS 0 or 1. Results: Of the 492 randomized patients, 491 had ECOG-PS 0 or 1 at baseline. The median OS was improved by 3.3 months with FTD/TPI plus bevacizumab (10.8 months with FTD/TPI plus bevacizumab vs 7.5 months with FTD/TPI), hazard ratio of 0.61 (95% CI, 0.49 to 0.77; P< 0.001), and median PFS was of 5.6 months vs 2.4 months favoring the FTD/TPI plus bevacizumab group (hazard ratio, 0.44; 95% CI, 0.36 to 0.54; P< 0.001). The results showed that FTD/TPI plus bevacizumab significantly improved time to ECOG-PS worsening from 0 or 1 to ≥2 when compared with FTD/TPI monotherapy (9.3 months with FTD/TPI plus bevacizumab vs 6.3 months with FTD/TPI (hazard ratio, 0.54; 95% CI, 0.43 to 0.67). Highest ECOG-PS distribution showed comparable proportions over cycles with no clinically meaningful difference ( > 10%) in both treatment arms. Considering patients who had discontinued study treatment as of the clinical cut-off date of July 5, 2022, 189/208 (91%) patients in the FTD/TPI plus bevacizumab and 200/235 (85%) patients in the FTD/TPI remained at ECOG-PS 0 or 1 at treatment discontinuation. In patients with maintained ECOG-PS, median OS demonstrated a prolonged survival in the FTD/TPI plus bevacizumab group vs the FTD/TPI group and a decreased death risk (10.58 months [range, 9.03 to 11.24] vs 8.71 months [range, 7.39 to 10.18]; hazard ratio, 0.78; 95% CI, 0.61 to 0.99). PFS consistently showed benefit in patients with maintained ECOG 0 or 1 favoring FTD/TPI plus bevacizumab (5.22 months [range, 4.17 to 5.75] vs 2.55 months [range, 2.1 to 3.58]; hazard ratio, 0.49; 95% CI, 0.4 to 0.61). Conclusions: Consistent with the results of the overall study population, FTD/TPI in combination with bevacizumab prolonged overall survival and PFS in patients with maintained ECOG-PS. Maintenance of performance status may allow patients to receive further therapeutic options during the continuum of care. Clinical trial information: NCT04737187 .