Application of XCELSIOR, a nationwide real-world observational research protocol, to identify efficacious targeted therapy regimens in advanced pancreatic adenocarcinoma.

e16245 Background: The proliferation of multi-omic diagnostics, highly selective targeted therapies, multi-modal immunotherapies, and personalized vaccines has yielded many promising novel combination regimens. Still, many patients with advanced cancer are left without clear options because the clinical efficacy of these regimens is based on anecdotal evidence as collective learning from real world practice is uncoordinated across the US. XCLESIOR ( NCT03793088 ) is a nationwide observational research protocol designed to efficiently gather, centralize, and standardize electronic medical records from any institution in the country, permitting complete longitudinal histories to be compiled for individual patients and analyzed on aggregate. Methods: Patients with pancreatic carcinoma were e-consented to XCELSIOR and real world data was entered into a 21 CF Part 11-compliant database and source-verified from raw electronic medical records generated in the standard practice of medicine including physician clinic notes, radiology reports, lab testing values, and genomics reports. Time-on-treatment and overall survival (OS) were calculated for cohorts based on treatment regimens containing chemotherapy, immunotherapy, or molecularly-targeted therapy. Results: As of February 1st, 2022, a total of 330 patients (pts) with pancreatic carcinoma had consented to XCELSIOR representing 199 institutions or oncology practices. 195 pts with metastatic pancreatic adenocarcinoma had longitudinal data structured and suitable for analysis at time of writing. Median follow-up from diagnosis was 1.3 years. The most prevalent treatment regimens were FOLFIRINOX (154 pts) and gemcitabine/nab-paclitaxel (139 pts). 28 pts were treated with targeted therapies and had significantly longer OS than pts that were never treated with targeted therapies (2.6 vs. 1.1 years median OS). Targeted therapies were most commonly employed at 3rd line (15/28) and 4th line (7/28), suggesting they benefitted pts following SOC chemotherapeutic regimens. Molecular targeted therapies utilized included primarily PARP inhibitors, MAPK pathway inhibitors, and HER2-targeted therapies. Time-on-treatment for FOLFIRINOX was median 105 days (generally 1st line), for gemcitabine/nab-paclitaxel was median 143 days (generally 2nd line), and for all targeted therapies was median 106 days. Conclusions: XCELSIOR is an efficient nationwide observational research protocol designed to aggregate, structure, and analyze longitudinal clinical data. Application of this virtual platform to an emerging metastatic pancreatic adenocarcinoma dataset suggested biomarker-based molecular targeted therapies utilized at 3rd and 4th line have the potential to be efficacious. Further stratification and analyses will be performed as the data matures. Clinical trial information: NCT03793088.