Abstract CT219: Neoadjuvant letrozole and palbociclib in stage II IIIB HR[/HER2[ breast cancer with Oncotype DX Recurrence Score(r)(RS) 18 25 or 26 100. Analysis of RS changes at surgery (DxCARTES trial)
Venue: Clinical Trials
Year: 2019

The combination of a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib) with an aromatase inhibitor (AI) significantly reduces Ki67 compared to single agent AI in the neoadjuvant setting, but the rates of pathological complete response (pCR) or residual cancer burden (RCB) 0 I remain modest. Despite this inadequate pathological downstaging, to date, there is no data about the efficacy of this treatment in terms of molecular downstaging detected by a more refined genomic signature than Ki67, such as the Oncotype DX Breast Recurrence Score(r) (RS) test. The aim of this trial is to validate the ability of neoadjuvant palbociclib plus letrozole to modify two initial intermediate or high RS tumor cohorts.  This is an international, multicenter, open label, non comparative, phase II trial. Main selection criteria include: (1) Pre or post menopausal women with treatment naive, centrally assessed, HR positive/HER2 negative, Ki67 20% and stage II IIIB breast cancer; (2) Pre treatment RS result 18; (3) Patients agree to collect tissue samples at screening, at Cycle 1 Day 14 of treatment, and at surgery. Patients will be allocated, according to the pre treatment RS result, either to Cohort A (RS 18 25) or Cohort B (RS 26 100) and will receive treatment with palbociclib (125 mg QD, 3/1 schedule) in combination with letrozole (2.5 mg QD, every 28 day cycle) LHRH analogs if pre menopausal status, for 24 weeks. Definitive breast surgery will be performed within 7 days after completion of 6 treatment cycles. The primary objective of the study is to explore the ability of palbociclib in combination with letrozole to induce global molecular changes, measured by either the post treatment RS result at surgery, or pCR. Secondary objectives include: (1) Concordance rate among post treatment RS result and RCB, Ki67, and preoperative endocrine prognostic index (PEPI) score; (2) Overall response rate; (3) Safety related outcome as per Common Terminology Criteria for Adverse Events v. 5.0. Patients will be accrued in a Simon's two stage design trial: optimal design in Cohort A and minimax design in Cohort B. With a unilateral type one error (alpha) set at 0.025 and a 0.8 power (type two error beta 0.2) the required number of evaluable patients are 28. Considering a drop out rate no lower than 10% a sample size of 33 patients in each cohort will be needed. First Patient First Visit: Expected on April 2019.  Antonio Llombart Cussac, Jose Perez Garcia, Angel Guerrero, Begona Bermejo, Miguel Gil, Vicente Caranana, Serafin Morales, Juan de la Haba, Maria Fernandez, Emilio Alba, Ander Urruticoechea, Lourdes Calvo, Mireia Margeli, Antonio Anton, Manuel Ruiz Borrego, Joan Albanell, Pedro Sanchez Rovira, Meritxell Bellet, Sofia Braga, Passos Coelho, Miguel Abreu, Javier Cortes. Neoadjuvant letrozole and palbociclib in stage II IIIB HR[/HER2[ breast cancer with Oncotype DX Recurrence Score(r) (RS) 18 25 or 26 100. Analysis of RS changes at surgery (DxCARTES trial) [abstract]  2019; 2019 Mar 29 Apr 3; Atlanta, GA. Philadelphia (PA) AACR;