Abstract 203TiP
Background
Adjuvant endocrine therapy (ET) is an effective treatment for hormonal receptor positive (HR+) HER2-negative (HER2-) early breast cancer (EBC) patients (pts). In high risk luminal EBC, chemotherapy (CHT) increases the probability of cure, at the cost of unwanted toxicities. Thus, the identification of pts for whom CHT may be spared is critical to improve management of treatment burden. Data from different adjuvant trials evaluating CDK4/6 inhibitors in intermediate to high-risk HR+ EBC led to conflicting results. Interestingly, data from NeoPAL (Cottu. Ann Onc) and SOLTI-1402 CORALLEEN (Prat. Lancet Onc) neoadjuvant trials suggested that a group of pts with high genomic risk could avoid CHT. Based on this, we hypothesize that CHT could be safely spared in pts with initial high-risk clinicopathological tumors that are converted to a low genomic risk of recurrence (ROR-low; Prosigna®) after neoadjuvant treatment with ribociclib (R) and letrozole (L) by continuing with this treatment in the adjuvant setting.
Trial design
RIBOLARIS is an open-label, multicenter international trial in 530 pts with HR+/HER2-, ki67≥20%, grade 2/3 and stage II EBC evaluating safety and long-term efficacy of a non-CHT treatment adjuvantly in pts with a biological response (ROR-low) to neoadjuvant R + L, consisting of six 28-days cycles of daily L and R (600 mg/day; 3W ON, 1W OFF). In pre-menopausal and male pts, LHRH agonists will be added. Adjuvant treatment will be decided according to centrally assessed ROR and pathological stage after surgery. Pts with ROR-low tumors will receive R (400 mg/day) in the adjuvant setting for 33 cycles. ET must be maintained for at least 5 years. Pts with ROR-med/high tumors will receive adjuvant CHT regimen followed by adjuvant R and ET. Primary endpoint is distant metastasis-free survival (DMFS) in the ROR-low cohort. Secondary enpoints include DMFS in the ROR-med/high cohort, invasive disease-free survival, pathological complete response and residual cancer burden. Two interim analysis are planned. Recruitment (53 sites in Spain, France and Portugal) started in April 2022.
Collaborators: UNICANCER, Breast International Group and NOVARTIS.
Clinical trial identification
NCT05296746