Cyclin-dependent kinase (CDK)4/6 inhibitors are approved for the treatment of early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer. The randomized NeoPAL and CORALLEEN trials established proof of the concept that CDK4/6 inhibitors combined with endocrine therapy (ET) can achieve efficacy comparable with multiagent chemotherapy in patients with the luminal B PAM50-based breast cancer subtype. The PAM50-derived risk of recurrence (ROR) score has emerged as a key endpoint for evaluating responses to neoadjuvant CDK4/6 inhibitors plus ET. New preliminary analysis of the RIBOLARIS trial demonstrates the potential to reduce ROR with neoadjuvant ribociclib.
RIBOLARIS (NCT05296746) is an open-label, single-arm, multicenter trial enrolling patients with high-risk (primary operable stage II, grade 2/3, Ki-67 ≥20%), HR-positive/HER2-negative breast cancer who are candidates for adjuvant chemotherapy. RIBOLARIS was designed to investigate whether patients achieving ROR-low disease after neoadjuvant ribociclib and ET (RIB-ET) could safely omit adjuvant chemotherapy. The trial assesses the safety and long-term efficacy of a nonchemotherapy regimen (RIB-ET) in patients whose tumors achieve an ROR-low score after 6 cycles of neoadjuvant RIB-ET (ribociclib 600 mg/day, 3 weeks on/1 week off, plus letrozole 2.5 mg/day ± luteinizing hormone−releasing hormone), followed by surgery within 10 days. Patients with ROR-medium/high tumors received chemotherapy-based treatment followed by RIB-ET (ribociclib at 400 mg). At least 40% of patients were expected to achieve an ROR-low score post-neoadjuvant treatment, estimating an enrollment goal of 1100 patients. A preplanned interim analysis was scheduled when reaching 300 patient-years of follow-up in the ROR-low cohort. This first interim analysis evaluated safety and efficacy after 686 surgeries of 750 patients.
At data cutoff, 686 of 1100 planned surgeries (62.4%) were completed. Of these, enrolled patients had the following baseline characteristics: median age, 57 years (interquartile range, 48-66); 61.8%, postmenopausal; 60.3%, tumor stage IIA; 59.6%, node-negative; and 74.4% and 24.9%, histological grade 2 and 3, respectively. A total of 361 patients (52.6%) achieved an ROR-low score (confidence interval [CI] 95%, 48.8%-56.4%), while 325 patients (47.4%) had ROR-medium/high scores (95% CI, 43.6%-51.2%). Mean ROR score (CI 95%) was 11.3 (10.5-12.2) in the ROR-low group and 36.9 (34.2-39.5) in the ROR-medium/high group. More patients, 157 (43.6%), were pre/perimenopausal in the ROR-low group than in the ROR-medium/high group, 103 (32.1%). At surgery, most patients were ypT1 and ypN0 across both groups. Breast-conserving surgery occurred in 278 patients (77.0%) and 228 (70.2%) in the ROR-low and -medium/high groups, respectively. Disease progressions are reported during neoadjuvant treatment in 15 of 686 patients. The most common grade 3 to 4 treatment-emergent adverse events were neutropenia (grade 3/4, 49.7%) and elevated transaminases (grade 3/4, 12.0%). Of 750 patients, a total of 126 patients (16.8%) discontinued due to any toxicity and 14 (1.9%) discontinuations were due to the investigator/sponsor’s decision.
Interim findings from the RIBOLARIS trial support and extend the results of the NeoPAL and CORALLEEN trials, demonstrating that a subset of patients with early-stage, HR-positive/HER2-negative breast cancer can achieve ROR-low disease after neoadjuvant RIB-ET, and may be considered candidates for chemotherapy omission. No new safety signals were identified, reinforcing the potential of RIB-ET as a safe and effective nonchemotherapy treatment strategy. Investigators report that recruitment is now complete.
Source: Cottu PH, Prat A, Pascual T, et al. Risk of recurrence (ROR) after neoadjuvant ribociclib plus ET in clinically high-risk ER+/HER2− BC: preliminary analysis of the SOLTI-RIBOLARIS trial. Presented at: ESMO Congress 2025. October 17, 2025; Berlin, Germany. Abstract 296O.