Background: Initial results from the KYT program demonstrated that 27% of PDACs harbor highly actionable molecular alterations (herein labelled “actionable biomarkers”), defined as biomarkers that predict for a high response rate to appropriately targeted tx, in any cancer type. Within this cohort, the median progression-free survival on molecularly-matched tx was 2 months longer than unmatched tx. Here, we present OS data emphasizing the 125 pts with “actionable biomarkers” who did or did not receive molecularly-matched tx. Methods: PanCAN and Perthera have coordinated tumor molecular profiling through commercial labs (NGS/IHC panels) for PDAC pts since 2014. Results are reviewed by a molecular tumor board, and tx options are prioritized based on the actionable biomarkers, in the context of the pt’s tx history. Pts are followed longitudinally to track physician tx choices and survival outcomes. Cox regression was used to assess differences in OS (measured from date of diagnosis until death). Results: Of 1053 pts who received a Perthera Report, 25% had “actionable biomarkers”. OS analyses across 454 pts with adequate tx history are shown in the Table below. Notably, pts with “actionable biomarkers” who received a molecularly-matched tx had a significantly increased OS compared to those with “actionable biomarkers” but who did not receive molecularly-matched tx. Subgroup analyses related to tx history and specific molecular pathways that warrant further investigation will be discussed. Conclusions: When the ~25% of PDAC pts whose tumors harbored “actionable biomarkers” received molecularly-matched tx, they had a better OS. These findings support the need to test all pts with PDAC, and just as importantly, to maximize access to molecularly-matched tx for appropriate pts, to achieve the best pt outcomes.