Background
Ribociclib demonstrated clinically and statistically significant progression-free survival (PFS) and overall survival (OS) benefits in 3 trials in patients with hormone receptor–positive (HR+)/HER2-negative (HER2–) advanced breast cancer (MONALEESA -2, -3, -7). We present an exploratory analysis of the MONALEESA trials of first-line patients with long-term response (LTR; PFS >4 y) to ribociclib and first-line postmenopausal patients with very long-term response (VLTR; PFS >5 y).
Methods
Pre- (MONALEESA-7) and postmenopausal (MONALEESA-2, -3) patients with HR+/HER2− advanced breast cancer received ribociclib plus endocrine therapy (ET) or placebo plus ET. Only patients who received first-line ribociclib were included in this analysis. Overall median follow-up was 6.1 years. Given the median PFS of approximately 2 years reported with first-line CDK4/6 inhibitor, more than doubling that time (PFS >4 y) was considered LTR; VLTR was PFS >5 years, calculated only for postmenopausal patients. Biomarker analyses were performed using baseline ctDNA and tumor samples.
Results
Of 666 patients treated with first-line ribociclib plus ET, 109 were on treatment at data cutoff. A total of 153 patients (23.0%) had LTR; 164 patients (24.6%) were censored before LTR cutoff. Median PFS (mPFS) in patients with LTR was 6.8 years (95% CI, 6.4-NE [not estimable]); median OS (mOS) was NE (95% CI, 7-NE). Age, body mass index, and menopausal status were balanced (Table). Similar proportions of premenopausal (34/150 [22.7%]) and postmenopausal patients (119/516 [23.1%]) had LTR. Patients with LTR were less likely than those with non-LTR to have liver metastasis (16.3% vs 25.5%) and less likely to have 3 or more metastatic sites (30.1% vs 43.0%). Similar proportions of patients with LTR vs non-LTR had bone-only disease (24.2% vs 19.5%). Patients with LTR had lower mean ctDNA fraction and were less likely to have CCND1 or TP53 alteration. They had lower gene expression of CCNE1 and a higher proportion of luminal A disease. Of 516 postmenopausal patients, 88 (17.1%) had VLTR.
Conclusions
In the MONALEESA studies, 1 of 4 patients treated with first-line ribociclib derived LTR (PFS >4y). Although LTR was more evident in patients with better prognostic factors, some patients with unfavorable prognostic factors still achieved LTR/VLTR. This exploratory analysis suggests long-term benefit with first-line ribociclib keeping a good number of patients with HR+/HER2− advanced breast cancer free of disease progression for more than 4 years.
Previously presented at 2025 SABCS: Andre F, et al. December 9-12, 2025; San Antonio, TX. Poster PD5-10. Reused with permission.
