Precision Oncology for Pancreatic Cancer across the United States: the Know Your Tumor ® experience

Abstract

Abstract The Know Your Tumor initiative identifies pancreatic cancer patients across the USA eligible for molecular testing through the Pancreatic Cancer Action Network call center. Perthera, Inc obtains patient consent, coordinates molecular testing, convenes a virtual molecular tumor board, prepares a report with a ranked list of therapy options, and collects outcomes. More than 1800 patients have been enrolled from 49 states and more than 1100 reports have been delivered. DNA testing was primarily with the Foundation Medicine panel of 324 genes and includes microsatellite instability (MSI). Therapy options include clinical trials, off-label treatments, or standard-of-care chemotherapy. Approximately one quarter (26%) of patients were identified with highly actionable (HA) alterations defined as molecular alterations for which a targeted therapy is indicated based on data in any cancer type. HA alterations include mutations in BRCA1/2, ATM, PALB2 and other DNA damage-repair genes indicating treatment with a PARP inhibitor, MSI-High with a PD-1 inhibitor, and alterations in RET, NTRK, BRAF, ALK, ROS, CDK4/6, FGF, and ROS with specific targeted agents. Patients treated in the advanced setting with HA alterations who received a molecularly-matched therapy (n = 46) had a significant 1-year improvement in overall survival compared to those with HA alterations who had no molecularly-matched therapies (HR = 0.42, p=.0004, n = 143) or those with no HA alterations (HR = 0.34, p=.000002, n = 488). Progression-free survival for those receiving a molecular matched therapy as 2nd line or greater therapy (10.93 mos, n = 38) was 2.4-fold greater than those with HA alterations and their best unmatched therapy (4.53 mos, p = 0.01, n = 84) and 2-fold greater than those without HA alterations (5.37 mos, p = 0.01, n = 288). These results provide evidence in a real-world setting that support the recent change in NCCN guidelines recommending tumor profiling for patients with advanced pancreatic cancer.