Trifluridine/tipiracil plus bevacizumab for third-line treatment of refractory metastatic colorectal cancer: The phase 3 randomized SUNLIGHT study.

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
Source: J Clin Oncol 41, 2023 (suppl 4; abstr 4) 10.1200/JCO.2023.41.3_suppl.4
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

In the SUNLIGHT study, Lonsurf + bevacizumab was found to be superior to bevacizumab alone in the 3L setting of mCRC, independent of mutation status. First 3L mCRC where the control group was an active compound instead of a placebo. OS was superior, with a clinically meaningful difference of 10.8 vs. 7.5 months. This is now the SOC 3L option in mCRC, in my opinion.


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.


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).


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.


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;

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