Abstract CT041: Anti-proliferative response and predictive biomarkers to palbociclib in early breast cancer: The Preoperative Palbociclib (POP) randomized trial
Authors: Arnedos Monica , Cheaib Bianca , Bayar Mohamed Amine , Michiels Stefan , Scott Veronique , Adam Julien , Leroux-Kozal Valerie , Marty Virginie , Mazouni Chafika , Sarfati Benjamin , Bieche Ivan , Gentien David , Delaloge Suzette , Lacroix-Triki Magali , Andre Fabrice 
Published: July 2016

Abstract
Background: In this monocentric randomized trial we aimed at identifying if short-term preoperative palbociclib treatment is associated with decreased proliferation and early biomarker changes in patients with early breast cancer (EBC) Methods: Untreated EBC patients were randomized 3:1 to oral palbociclib 125mg daily for 14 days until the day before the surgery vs no treatment. FFPE and frozen samples were extracted at baseline and at surgery. Primary objective was antiproliferative response defined as a natural logarithm of Ki67 expression at day 15 below 1. Immunostaining (Ki67, RB, pRB, p16, pAKT, pER), FISH (CCND1) and gene expression (GE) arrays were performed pre- and post-treatment. PIK3CA and AKT1 mutations were assessed pretreatment. Results: 74 patients were randomized in the palbociclib arm and 26 in the control arm. 93% tumors were HR-positive; 8% HER2-positive. Palbociclib treatment led to significantly more patients with antiproliferative response as compared to control (58% vs 10%, p = 0.0003). In addition, mean decrease from baseline in ln(Ki67) was significantly higher at day 15 in the palbociclib arm (p&lt;0.0001). In patients with HR+/Her2-, palbociclib decreased Ki67 in 72% of the patients (vs 5% in control). No Ki67 response was observed in TNBC or Her2-positive tumors (interaction test, p = 0.0038). Palbociclib significantly decreased p-Rb as compared to control (p = 0.0027, ANCOVA model). Baseline Rb (interaction test, p = 0.36), pRb (p = 0.89) and p16 (p = 0.13) did not predict palbocicilb effect on Ki67. Palbociclib effect in ki67 correlated with changes in pRB from baseline (Spearman rank correlation r = 0.42, p&lt;0.0001). Additional analyses are ongoing (CCND1 amplification, GE, pAKT, pER, PIK3CA, AKT1) Conclusions: Short-term pre-operative Palbociclib treatment in EBC patients significantly decreased Ki67. This effect depended on molecular subtypes and correlated with changes in pRB, suggesting that bioactivity of palbociclib could be the main determinant of his short term effect on proliferation. Mechanisms of tumor adaptation to CDK4/6 inhibitors (GE, pAKT, pER) are being investigated and will be presented.
Citation Format: Monica Arnedos, Bianca Cheaib, Mohamed Amine Bayar, Stefan Michiels, Veronique Scott, Julien Adam, Valerie Leroux-Kozal, Virginie Marty, Chafika Mazouni, Benjamin Sarfati, Ivan Bieche, David Gentien, Suzette Delaloge, Magali Lacroix-Triki, Fabrice Andre. Anti-proliferative response and predictive biomarkers to palbociclib in early breast cancer: The Preoperative Palbociclib (POP) randomized trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT041.