Neoadjuvant endocrine therapy (NET) is a standard approach for elderly – unfit patients with an Endocrine Receptor positive Early Breast Cancer (EBC). However, for younger – fit patients this option is not generally considered because of scientific limitations when compared to chemotherapy. In fact, endocrine therapy, even in combination with other agents has not shown significant pathologic complete responses in this scenario.
In recent years, the role of chemotherapy has been questioned in patients with EBC luminal phenotype (ER[+], HER2[-]) because of its modest benefit for the whole population. Molecular tests to identify patients achieving the greatest or modest benefit from chemotherapy have been generated. The Oncotype DX Breast Recurrence Score® test is the only to show both a prognostic and predictive value. In general, a low Recurrence Score (RS) (<26 for postmenopausal and <21 for premenopausal) identifies patients that will not achieve significant benefit from adjuvant chemotherapy.
DxCARTES is an international, multicentre, open-label, non-comparative, Simon’s two-stage design, phase II clinical trial. The study explores the late molecular-prognostic RS changes achieved with palbociclib, a Cyclin Dependent Kinase 4 and 6 inhibitor (CDK4/6i), in combination with letrozole in patients with Early Breast Cancer (EBC).
Patients require to have a non-previously treated Stage II-III EBC with ER/PR[+] and HER2[-] criteria as well as a high KI67 (>20%). All candidate tumor samples will be tested with the Oncotype DX Breast Recurrence Score®; and those with an aggressive RS (>18) will be finally selected for the study. Two cohorts will be recruited according to RS results (18-25 and 26-100).
All patients will complete a 6-month neoadjuvant palbociclib-letrozole treatment (with LHRH-Ag if premenopausal) in the absence of early progression. At surgery, a second tumor sample will be required (in the absence of pCR) for a second Oncotype DX Breast Recurrence Score® test. The pathology report will also be captured, including PEPI and RCB analysis. The primary objective is to analyze Intra-patient RS changes in both intermediate and high-risk RS groups.
The hypothesis behind the study design relates to the lack of pathological tumor downstaging observed with NET (with or without CDK4/6i) in several clinical trials. In contrast, the benefit of ET in this population is much greater than the one obtained with chemotherapy, meaning that the mechanism driven this benefit may be related to molecular changes that decrease the aggressiveness of the tumor.
The DxCARTES trial poster was presented at the American Association for Cancer Research Congress (AACR) hold in Atlanta on March 29 to April 3, 2019.
Author: Andrea Malfettone