A Preclinical Trial To Evaluate Therapies For Brca-Associated Pancreatic Cancer.

332Background: Pancreatic ductal adenocarcinoma (PDAC) associated with germline BRCA1 or BRCA2mutations may have selective sensitivity to agents that exploit homologous recombination DNA repair defects. We hypothesized that cisplatin, a DNA-crosslinking agent, and talazoparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, monotherapies are efficacious in BRCA-associated PDAC, while combination therapies with these agents have enhanced efficacy. Methods: A preclinical trial was performed in subcutaneous patient-derived tumor xenograft (PDX) mouse models with (n = 5) and without (n = 2) germline BRCA1 or BRCA2mutations. Mice harboring PDX tumors were treated with vehicle, talazoparib, cisplatin, gemcitabine, talazoparib with cisplatin (TC), talazoparib with gemcitabine (TG), or cisplatin with gemcitabine (CG). Twelve tumors were randomized into each trial arm, treated for 28 days, and then monitored without further treatment to assess tumor regrowth. Results: Treatment with cisplatin and talazoparib monot...