Phase Ii Trial Of Palbociclib (Pd-0332991) In Patients With Metastatic Urothelial Cancer (Uc) After Failure Of First-Line Chemotherapy.

500Background: UC is a common malignancy with poor outcomes in patients with metastatic disease. The majority of urothelial cancers harbor alterations in key retinoblastoma (Rb) pathway genes with CDKN2A alterations in approximately 35% of tumors, leading to loss of Rb tumor suppressor function with subsequent cell cycle progression and unchecked cell proliferation. Palbociclib is an oral, selective inhibitor of CDK4/6 that prevents Rb phosphorylation to promote cell cycle arrest. Methods: In this phase II trial, biomarker-selected (p16 loss and intact Rb by tumor immunohistochemistry [IHC]) patients with metastatic platinum-refractory UC received palbociclib 125mg po daily for 21 days of a 28-day cycle. The primary endpoint was progression-free survival at 4 months (PFS4) using a Simon’s two-stage design. Prespecified tumor analysis with next generation sequencing (NGS) including Rb pathway alterations was conducted. Results: 12 patients (67% male, median age 68 years) were enrolled. Post-platinum progno...