Despite the improvement in the treatment of early-stage breast cancer (BC) with chemotherapy, many patients have residual disease with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pathological complete response (pCR), particularly in highly proliferative tumors. In HR+ BC, the pCR rates after NAC are around 10-15%. Additional therapeutic strategies to eradicate these residual tumor cells are needed. The combination of cyclin-dependent kinase inhibitors with first or second-line endocrine therapy are options for metastatic BC and its role in the early-setting is being evaluated in several studies. Posttreatment Ki67 levels provide prognostic information for patients with HR+ BC and residual disease, but the prospective validation of this biomarker is necessary. We hypothesize that palbociclib plus letrozole offers antiproliferative benefit in the pre-surgery setting for patients with residual disease and high risk of recurrence.
SOLTI1710 PROMETEO II is a prospective single-arm window of opportunity trial in HR+/HER2-negative operable BC patients with residual disease after NAC designed to evaluate the biological effect of palbociclib plus letrozole and to identify biomarkers for better patient selection. Patients must have histologically confirmed HR+/ HER2-negative tumors and locally assessed baseline Ki-67 > 10%, have completed ≥80% total dose of an anthracycline/taxane-based NAC; and residual disease ≥ 1 cm by magnetic resonance imaging and Ki67% ≥ 10% after NAC. Patients will be administered palbociclib at a dose of 125 mg/day, 3 weeks on/1 week off and letrozole 2.5 mg/day continuously, one cycle of treatment. After the neoadjuvant treatment, patients will undergo surgery. Tumor tissue and blood samples will be collected for correlative translational studies. The primary endpoint is the Complete Cell Cycle Arrest (CCCA) determined by Ki67<2.7%, centrally assessed at surgery. Secondary endpoints include rate of RCB 0/1 and pCR after neoadjuvant treatment and adverse events. Recruitment of the planned 20 patients is ongoing in 8 sites across Spain.
Clinical trial identification
Legal entity responsible for the study
SOLTI Breast Cancer Research Group.
E.M. Ciruelos: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. X. González-Farré: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Eisai. P. Villagrasa: Speaker Bureau/Expert testimony: NanoString. A. Prat: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Lilly; Advisory/Consultancy: NanoString; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Oncolytics; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Puma; Advisory/Consultancy: BMS. S. Pernas Simon: Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Poliphor. All other authors have declared no conflicts of interest.