Abstract PD5-10: Pooled analysis of patients (pts) treated with 1st-line (1L) ribociclib (RIB) + endocrine therapy (ET) in the MONALEESA (ML) studies: long-term progression-free survival (PFS)

Abstract Background: RIB demonstrated clinically and statistically significant PFS and overall survival (OS) benefit in all of its phase 3 trials in HR+/HER2− advanced breast cancer (ABC; ML-2, -3, -7). We studied clinical characteristics and biomarkers of pts who derived long-term treatment benefit. We present an exploratory analysis of the ML trials of all 1L pts with long-term response (LTR; PFS >4 y) to RIB and 1L postmenopausal pts with very long-term response (VLTR; PFS >5 y). Methods: In the ML trials, pre- (ML-7) and postmenopausal (ML-2, -3) pts with HR+/HER2− ABC received RIB + ET or placebo + ET. Only pts who received 1L RIB were included in this pooled analysis. Pts with early relapse (treatment-free interval [TFI] ≤12 months on [neo]adjuvant ET) and those in ML-7 treated with tamoxifen were excluded. Overall median follow-up (mfu) was 6.1 y (ML-2, 6.7 y; ML-3, 5.9 y; ML-7, 4.5 y). Given the median PFS of ≈2 y reported with CDK4/6i in 1L ABC, more than doubling that time (PFS >4 y) was considered LTR. VLTR was defined as PFS >5 y, calculated only for postmenopausal pts (ML-2, -3) as mfu in ML-7 was <5 y. Biomarker analyses were performed using baseline ctDNA and tumor samples. Nominal P values (unadjusted) were calculated to compare characteristics of pts with LTR and non-LTR. Results: Of 666 pts treated with 1L RIB + ET included in the analysis, 109 were on treatment at data cutoff. A total of 153 pts (23.0%) had LTR; 164 pts (24.6%) were censored before LTR cutoff. Median PFS (mPFS) in pts with LTR was 6.8 y (95% CI: 6.4 y-NE [not estimable]); median OS (mOS) was NE (95% CI: 7 y-NE). Age, body mass index, and menopausal status were balanced between pts with LTR and non-LTR ( Table ). Similar proportions of premenopausal (34/150 [22.7%]) and postmenopausal pts (119/516 [23.1%]) had LTR. Pts 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 metastatic sites (30.1% vs 43.0%). Similar proportions of pts with LTR vs non-LTR had bone-only disease (24.2% vs 19.5%). ctDNA analysis used a panel of 558 genes; gene expression analysis used 800 genes. Pts with LTR had a lower mean ctDNA fraction and were less likely to have CCND1 or TP53 alteration detected by ctDNA. Additionally, they had lower gene expression of CCNE1 and a higher proportion of luminal A disease (PAM50 based). Of 516 postmenopausal pts, 88 (17.1%) had VLTR; further analysis will be provided in the presentation. Conclusions: In the ML studies, 1 of 4 pts treated with 1L RIB were able to derive LTR (PFS >4 y). Pts with LTR had mPFS of 6.8 y, and mOS was NE. Although LTR was more evident in pts with better prognostic factors, noticeably, some pts with unfavorable prognostic factors were still able to achieve LTR. This exploratory analysis suggests long-term benefit with 1L RIB in keeping a good number of pts with HR+/HER2− ABC free of disease progression for more than 4 y. Citation Format: F. Andre, P. A. Fasching, A. Prat, P. Neven, Y. Lu, A. Bardia, G. Curigliano, V. Kaklamani, P. Razavi, Y. Yap, F. Su, E. Roux, K. Pantoja, J. Wu, A. Lteif, D. Juric. Pooled analysis of patients (pts) treated with 1st-line (1L) ribociclib (RIB) + endocrine therapy (ET) in the MONALEESA (ML) studies: long-term progression-free survival (PFS) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD5-10.