Author(s): Josep Tabernero, Gerald W. Prager, Marwan Fakih, Fortunato Ciardiello, Eric Van Cutsem, Elena Elez, Felipe Melo Cruz, Lucjan Wyrwicz, Daniil Stroyakovskiy, Zsuzsanna Papai, Pierre-guillaume Poureau, Gabor Liposits, Chiara Cremolini, Igor Bondarenko, Dominik Paul Modest, Karim A. Benhadji, Ronan Fougeray, Catherine Leger, Nadia Amellal, Julien Taieb
BACKGROUND
Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (Bev) demonstrated promising efficacy in a randomized phase 2 trial of heavily pretreated patients (pts) with metastatic colorectal cancer (mCRC). SUNLIGHT was conducted to confirm these findings.
METHODS
The global phase 3 SUNLIGHT study enrolled pts aged ≥18 years with histologically confirmed mCRC, ECOG PS 0/1, and treated with 1-2 prior chemotherapy regimens in an advanced setting, including fluoropyrimidines, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody (if medically considered) and/or anti-EGFR monoclonal antibody for RAS wild-type tumors. Pts were randomised (1:1) to receive FTD/TPI (35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle) alone or combined with Bev (5 mg/kg on days 1 and 15). Primary endpoint was overall survival (OS).
RESULTS
Between Nov 2020 and Feb 2022, 492 pts were randomised to receive FTD/TPI + Bev (n = 246) or FTD/TPI (n = 246). Baseline characteristics were balanced between arms. FTD/TPI + Bev significantly extended OS over FTD/TPI, median OS was 10.8 months vs 7.5 months, respectively (HR, 0.61; 95% CI, 0.49, 0.77; P< 0.001). OS rates at 12 months were 43% in the FTD/TPI + Bev arm and 30% in the FTD/TPI arm. Median progression-free survival was 5.6 months in the FTD/TPI + Bev arm and 2.4 months in the FTD/TPI arm (HR, 0.44; 95% CI, 0.36,0.54; P< 0.001). Grade ≥3 adverse events (AEs) were not significantly increased in the FTD/TPI + Bev arm vs the FDT/TPI arm (72.4% vs 69.5%). No new safety signals were noted.
CONCLUSIONS
FTD/TPI + Bev provided a statistically significant and a clinically meaningful 3.3-month improvement in OS, extending mOS up to 10.8 months, with a 39% reduction in the HR of death in pts with refractory mCRC and with a predictable and acceptable safety profile. Clinical trial information: NCT04737187.
Author Affiliations
Vall d’Hebron Hospital Campus and Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, Barcelona, Spain; , Medical University of Vienna, Vienna, Austria; , City of Hope National Comprehensive Cancer Center, Duarte, CA; , Precision Medicine Department, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy; , Department of Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Herent, Belgium; , Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), UVic-UCC, Barcelona, Spain; , Núcleo de Pesquisa e Ensino da Rede São Camilo, Sao Paulo, Brazil; , Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Cancer Research Institute, Warsaw, Poland; , Moscow City Oncological Hospital #62, Moscow Area, Russian Federation; , Medical Oncology, Duna Medical Centre, Budapest, Hungary; , Institut de Cancérologie, Brest, France; , Department of Clinical Research, University of Southern Denmark, Odense, Denmark; , Department of Translational Research and New Technologies, University of Pisa, Pisa, Italy; , Department of Oncology and Medical Radiology; Dnipropetrovsk Medical Academy, Dnipro, Ukraine; , Charité Universitätsmedizin Berlin, Berlin, Bagun, Germany; , Taiho Oncology, Inc., Princeton, NJ; , Servier International Research Institute, Suresnes, France; , Université Paris-Cité, (Paris Descartes), Georges Pompidou European Hospital, SIRIC CARPEM, Paris, France;
