Palbociclib Versus Placebo In Combination With Letrozole For Patients With Advanced Or Recurrent Endometrial Cancer: The Nsgo Engot-En3/Paleo Trial.

TPS5612 Background: Endometrial cancer (EC) patients with advanced or recurrent disease and endometrioid histology have a short progression-free survival (PFS). These malignancies are hormone dependent and endocrine therapy with aromatase inhibitors is well established. Palbociclib is an oral and selective inhibitor of cyclin-dependent kinases CDK4 and CDK6. Studies in breast cancer have demonstrated superiority of letrozole treatment in combination with palbociclib vs. letrozole monotherapy in oestrogen receptor positive (ER+) HER2- advanced disease. The combination is generally well tolerated with an acceptable toxicity profile. This multicenter, prospective, double-blind, placebo-controlled, randomized, phase II trial is evaluating the efficacy of letrozole when combined with palbociclib against letrozole-placebo combination therapy in women with ER+ advanced or recurrent EC. Methods: The primary objective of this trial is to demonstrate superiority of palbociclib against placebo in combination with letrozole, as defined by investigator-assessed progression-free survival (PFS). Key eligibility criteria include: histologically confirmed ER+ EC of endometrioid type; stage 4 or recurrent disease; prior surgery, adjuvant chemotherapy, radiation therapy, hormonal therapy (e.g. megestrol acetate) is permitted; measurable/evaluable disease according to RECIST 1.1. 78 patients will be randomized 1:1 to receive palbociclib 125mg daily or placebo on days 1-21 and letrozole 2.5mg daily on days 1-28 in a 28 days cycle until disease progression, unacceptable toxicity, or withdrawal. Secondary endpoints include PFS in sub-populations, overall response rate, disease control rate, PFS2, time to first subsequent therapy, time to second subsequent therapy, overall survival, safety & tolerability, patient reported outcomes (assessed via EORTC QLQ-C30 and EORTC QLQ-EN24) and PFS in patients with or without retinoblastoma protein-expressing tumors. The following cooperative groups are participating: NSGO (DK, FIN, NOR), MITO (ITA), GEICO (SPA) & NOGGO (GER). Clinical trial information: NCT02730429.