Emulation of the SUNLIGHT Trial Using Specialty Oncology Electronic Health Records Databases

Randomized controlled trials (RCTs) are generally regarded as the gold-standard of evidence for establishing efficacy of medical products. However, real-world data (RWD) are increasingly used to complement evidence from RCTs. Yet, to have confidence in the accuracy of non-interventional studies of medical products and their outcomes in oncology, investigators need to know what questions can be validly answered, with which non-interventional study designs, and which analysis methods are appropriate, given the data that is available. Building on a process from the RCT DUPLICATE initiative, EmulatioN of Comparative Oncology trials with Real-world Evidence (ENCORE) is the trial emulation discussed in this protocol, which is part of the expansion project specific to oncology and aims to emulate 12 randomized oncology RCTs using multiple EHR data sources. The purpose of this protocol is to describe the emulation of the SUNLIGHT trial.5 SUNLIGHT was a Phase III, open-label, randomised study assessing the efficacy and safety of trifluridine-tipiracil (FTD-TPI) (35 mg/m²/dose orally BID; Given 5 days on / 2 days off schedule, for 2 weeks, followed by 14-day rest) plus bevacizumab (5 mg/kg intravenously on Day 1 and Day 15, every 4-week cycle) versus FTD-TPI alone (35 mg/m²/dose orally BID; Given 5 days on / 2 days off schedule, for 2 weeks, followed by 14-day rest) in patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer.