Evaluation Of Parp Inhibition As A Platinum Sparing Strategy In Brca2-Deficient Pancreatic Tumors.

e15237 Background: BRCA1/2 mutations are found in up to 5% of patients with PAC. PARP inhibitors (PARPi) and platinum based chemotherapy may have increased anti-tumor efficacy in this population due to deficient DNA repair by homologous recombination (HR). We evaluated the use of cisplatin (CDDP) alone and in combination with the PARPi Olaparib (Ola) in a Brca2deficient murine model of PAC. Methods: KrasG12D/+; p53R270H/+; Pdx-1-Cre; Brca2mut mice were generated as previously described. Experimental mice began treatment at day 30 +/- 2 days with intraperitoneal (IP) CDDP 6mg/kg every 21 days with Ola 50mg/kg IP daily 5 days/week (n=11) or vehicle (n=11). A further 7 mice received Ola alone at same schedule and 8 mice received vehicle only. Pancreatic imaging was performed by T2 weighted MRI at regular intervals. For CDDP treated mice, treatment was held after dose #4 in the absence of visible pancreatic tumor on MRI for toxicity concerns and reinstated only at time of tumor growth. Mice were euthanized fo...