Genomic-directed personalized matched targeted therapy approach may improve clinical outcomes among patients with advanced pancreatic cancer.

Abstract

e16794 Background: Despite advances in pancreatic cancer management, 2-year overall survival (OS) remains to be less than 10% in patients with metastatic disease. Given this, novel therapeutic approaches are urgently needed. We hypothesize that a matched combination targeted therapy approach, which is customized based on patient’s cancer genomics, may have clinical efficacy among advanced pancreatic cancer patients. Methods: This is a single center retrospective analysis of advanced pancreatic adenocarcinoma patients treated at UC San Diego. All patients (N = 26) received matched targeted therapy based on genomic alterations detected by tissue NGS and/or blood cell-free DNA assays. This study followed the guidelines of the IRB-approved UCSD PREDICT study (NCT02478931). Results: In the cohort, median age was 67 and 62% (N = 16) were female. 27% (N = 7) received matched therapy front line and 73.1% (N = 19) received matched therapy in the second line or later. The median number of targeted agents administered was 3 (range 1-4). There was a significant improvement in progression-free survival (PFS) when matched therapy was administered in the first line when compared to second line or greater (7.0 vs 2.8 months, hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.19-0.90, P = 0.031) and there was a difference in OS (1st line vs 2nd line or greater: 9.2 vs 4.4 months, HR: 0.58, 95% CI: 0.24-1.42, P =0.23). When stratified by Matching Score of ≥50% (high) and < 50% (low) (Matching Score is roughly equivalent to the number of alterations targeted by therapy divided by the total number of characterized alterations), patients who were treated with a high Matching Score demonstrated significantly prolonged PFS and OS when compared to those with a low Matching Score (PFS: 3.8 vs 2.0 months, HR: 0.34, 95% CI: 0.13-0.91, P =0.031, OS: 5.6 vs 3.3 months, HR: 0.33, 95% CI: 0.13-0.85, P =0.022). In patients with a Matching Score of ≥50%, the disease control rate (DCR) (defined as complete response, partial response, and stable disease ≥ 6 months) was 36.8% and among patients who received matched therapy first line, DCR was 71.3%. Representative cases who were successfully treated with matched targeted therapy will be presented. Conclusions: Combination matched targeted therapy, particularly in patients with a high degree of matching, showed improved clinical outcomes. While the sample size here is small and these data warrant further prospective investigation, matched combinatorial targeted therapy may offer patients a novel option for therapy.