Abstract A36: Assessment of effectiveness and molecular markers of CDK4/6 inhibitor Palbociclib in Pancreatic Ductal Adenocarcinomas

Pancreatic Ductal Adenocarcinoma (PDAC) continues to be the deadliest human cancer with a 5-year survival rate of 7%. One of the current standards of care for advanced PDAC is gemcitabine plus nab-paclitaxel, a regimen our group helped develop. Finding new agents to combine with this regimen remains necessary, particularly using drug targeting strategies. At the molecular level, genetic and genomic profiling identified CDKN2A as a very frequently disrupted gene in PDAC ( In the current study, we aimed to evaluate the effectiveness of palbociclib monotherapy and in combination with nab-paclitaxel and gemcitabine/nab-paclitaxel in a cohort of PDACs patient derived xenograft (PDX) models. PDX models obtained from late stage PDAC patients were treated with palbociclib alone and in combination with gemcitabine/nab-paclitaxel. The majority of models displayed >50% tumor growth inhibition (TGI) following treatment with single agent palbociclib. Treatment with palbociclib plus nab-paclitaxel or palbociclib plus gemcitabine/nab-paclitaxel increased TGI to a greater degree than the gemcitabine/nab-paclitaxel combination and also increased the duration of response as compared to the standard of care therapy. Moving forward, the palbociclib/nab-paclitaxel combination will be evaluated in a clinical trial for PDAC patients. We are currently expanding our analyses to a larger cohort of PDX models and performing molecular characterization of these models in order to gain insights on biomarkers and mechanism of action of the drug combinations in PDAC. Citation Format: Beatriz Salvador, Pedro P. Lopez-Casas, Camino Menendez, Natalia Banos, Francesca Sarno, Yin Min-Jean, Peter Olson, Todd VanArsdale, David J. Shields, Manuel Hidalgo. Assessment of effectiveness and molecular markers of CDK4/6 inhibitor Palbociclib in Pancreatic Ductal Adenocarcinomas. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A36.