Assessing real-world survival outcomes of patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line FOLFIRINOX compared to patients from a phase 1/2 trial treated with NALIRIFOX.
Authors: Zhu Xuelian , Cockrum Paul , Shah Bonny , Parzynski Craig , Garawin Tamer , Maxwell Fiona , Surinach Andy 
Published: June 2021

e16252 Background: Treatment options remain limited for pts newly diagnosed with mPDAC. NCCN and ASCO guidelines both recommend treatment with FOLFIRINOX or gemcitabine plus nab-paclitaxel in the first line (1L) setting for pts with mPDAC and good performance status. Over 80% of randomized clinical trials (RCTs) studying treatments for mPDAC have failed to meet their primary endpoints. Recently published analyses have utilized real-world (RW) data to compare outcomes between pts enrolled in clinical trials and RW pts. This study sought to identify the eligible population of pts with mPDAC treated with FOLFIRINOX in the 1L setting who would meet RCT eligibility criteria for the phase 1/2 study (NCT02551991) evaluating NALIRIFOX for pts with previously untreated locally advanced or mPDAC, and to assess their survival outcomes. Methods: This retrospective observational study utilized the Flatiron Health EHR database. Data were analyzed for adult pts diagnosed with mPDAC between January 2016 and February 2020 who initiated treatment with FOLFIRNOX in 1L within 90 days of their diagnosis for metastatic disease. Eligibility criteria from the phase 1/2 trial were applied to select a population of RW pts who may have been eligible to enter the RCT. Pts meeting the following criteria were included: good performance scores (ECOG 0-1), adequate hematological, hepatic, and renal function, were recovered from the effects of surgery, were untreated in the year prior to initiating 1L, and had no evidence of a different cancer in the last three years. Kaplan-Meier analyses were used to assess the median overall survival (mOS) from the start of 1L FOLFIRNOX treatment. Results: Of the 1,210 pts treated with 1L FOLFIRINOX, 652 pts (53.8%) met less stringent versions of the RCT eligibility criteria in which missing values were deemed to indicate normal function/performance; 244 pts (20.2%) met the more stringent criteria and had complete data. The most restrictive selection criteria were the requirements for adequate hematological, hepatic, and renal function and having received prior therapy. The median age at treatment initiation among the 244 pts was 64 years (IQR: 58 – 70). 153 pts were male (62.7%), 158 were White (64.8%), and ECOG scores of 0 and 1 were split among the cohort 50%/50%. The mOS observed for the 244 pts was 10.1 months (95% CI: 9.1 – 11.3). The reported mOS from the phase 1/2 trial of NALIRIFOX was 12.6 months (8.7 – 18.7). Conclusions: This study demonstrates that RW data may be used to select a comparator cohort for a clinical trial. Initial estimates suggest NALIRIFOX pts from the RCT experienced longer survival than those receiving 1L FOLFIRINOX in the RW setting. Further analysis is necessary to minimize the effects of confounding and the differences in data collection between the RW and the RCT settings.