Genomic tests in oncology can analyze a tumor sample to determine the activity of certain genes to give information on how likely a tumor is to grow and spread. In breast cancer, the Oncotype DX Breast Recurrence Score (RS) Test is a useful tool that evaluates 21 genes to determine how likely early-stage breast cancer is going to progress as well as how it will respond to certain treatment. It is utilized to determine if chemotherapy is necessary. Eligibility for this test requires the breast cancer to be estrogen-receptor-positive (ER+) and HER2 negative.
Cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy frequently leads to complete cell cycle arrest in luminal early-stage breast cancer, but rates of pathological complete response (pCR) and residual cancer burden are modest. Furthermore, whether the addition of neoadjuvant CDK4/6i to endocrine therapy has an effect of molecular downstaging assessed by the 21-gene RS assay remains undetermined. Identifying patients that have switched from high-risk to low-risk RS after neoadjuvant CDK4/6i plus endocrine therapy could help further identify patients who do not need adjuvant chemotherapy. Therefore, the DxCARTES trial aims to evaluate the biological effect and clinical activity of neoadjuvant administration of Palbociclib in combination with letrozole in patients with HR+/HER2- stage II-IIIB luminal B-like early breast cancer based on their RS score.
The study is a multicenter, open-label, two-arm, non-comparative, phase II trial. The 21-gene RS score was determined at baseline and patients were stratified into either Cohort A: RS 18-25 or Cohort B: RS 26-100. The co-primary endpoints for the study are the rate of patients in each cohort who achieved a RS<21 or a pCR in the breast axilla or microscopic residual infiltration (if RS was not feasible at surgery) after neoadjuvant treatment. The study is also assessing the rate of patients in either cohort who had a pCR in the breast (pCRB: ypT0/Tis) at time of surgery, the change in RS rates, RCB  0–1, preoperative endocrine prognostic index (PEPI) score of 0, conversion from mastectomy to breast-conserving surgery (BCS) and from N1 to N0, the concordance rate between RS and CCCA (Ki67≤2.7%), the best response, the overall response, safety and tolerability, and the Ki67 expression rates at baseline, C1D15, and surgery.
Preliminary results were presented at the San Antonio Breast Cancer Symposium 2021 and showed that at surgery, 66.7% of patients in cohort A had a RS stabilization (RS ≤25), failing to reach the primary endpoint (set for 76% of patients, 25/33), whereas 52.9% of patients in cohort B had RS ≤25 or a pCR after treatment, meeting the primary endpoint (positive findings for 24% of patients 8/33).
The study is recruiting 66 patients in 16 sites across Spain. Contact us if you want to learn more!