Abstract PS1-10-27: Progression-free survival (PFS) and overall survival (OS) results from the phase 3 MONALEESA-3 trial of postmenopausal patients with hormone receptor-positive (HR+)/HER2-negative (HER2−) advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL): A subgroup analysis of patients with invasive lobular carcinoma (ILC)

Abstract Background: The phase 3 MONALEESA-3 trial reported a statistically significant improvement in PFS with RIB + FUL over placebo (PBO) + FUL as first-line (1L) or second-line (2L) treatment (tx) in postmenopausal patients with HR+/HER2- ABC at the primary analysis (median: 20.5 months vs 12.8 months; HR: 0.59; 95% CI: 0.48-0.73; P < 0.001). Additionally, a statistically significant OS benefit with RIB + FUL was seen at the final protocol-specified analysis (HR: 0.72; 95% CI: 0.57-0.92), which was maintained with extended follow up (median follow-up time: 56.3 months; HR, 0.73; 95% CI: 0.59-0.90). Patients with the ILC subtype, who account for 10-15% of all breast cancer patients, show unique clinicopathological characteristics. This exploratory analysis examined the PFS and OS in a subgroup of MONALEESA-3 patients with ILC, including those receiving tx in the 1L setting. Methods: Postmenopausal patients with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL in 1L and 2L settings. PFS and OS were evaluated by log-rank test and Cox proportional hazards model stratified per interactive response technology by lung/liver metastasis status and previous endocrine therapy. PFS and OS were summarized using Kaplan-Meier methods. The data cutoff for this analysis was January 11, 2023. Results: Among all MONALEESA-3 patients (N=726), 120 (16.5%) had the ILC subtype, 77 of whom were treated with RIB + FUL and 43 with PBO + FUL. Additionally, of the 354 MONALEESA-3 patients receiving 1L tx, 56 (15.8%) had the ILC subtype, with 38 treated with RIB + FUL and 18 with PBO + FUL. Patient demographics and disease characteristics were balanced between the two tx arms in this subgroup. Patients had a median age of 63 y (RIB arm: 64 y; PBO arm: 63 y); 17.5% of patients had de novo ABC (RIB arm: 18.2%; PBO arm, 16.3%), and 81.7% patients had experienced relapse >12 months after completion of (neo)adjuvant therapy (RIB arm: 80.5%; PBO arm, 83.7%); 83.3% of patients had bone metastasis (RIB arm: 81.8%; PBO arm, 86.0%), and 45.0% had visceral metastasis (RIB arm: 48.1%; PBO arm: 39.5%). The baseline characteristics were similar among those with ILC receiving 1L tx and remained balanced between the two tx arms. Patients with ILC receiving RIB + FUL showed a longer PFS (median: 20.5 months) than those receiving PBO + FUL (median: 9.4 months, HR: 0.56; 95% CI: 0.37-0.86). The median PFS was further prolonged in patients with ILC receiving 1L tx with RIB + FUL (median: 26.3 months) over PBO + FUL (median: 18.1 months; HR: 0.78; 95% CI: 0.39-1.59). Additionally, patients with ILC receiving RIB + FUL had a longer OS (median: 51.2 months) than those receiving PBO + FUL (median: 30.8 months, HR: 0.62; 95% CI: 0.39-0.98); the median OS in patients with ILC receiving 1L tx with RIB + ET vs PBO + FUL was 59.6 months vs 40.0 months (HR: 0.54; 95% CI: 0.25-1.19). Rates of adverse events (AEs) including neutropenia, alanine aminotransferase elevation, and aspartate aminotransferase elevation in RIB + FUL-treated patients in the ILC subgroup (and in the 1L tx ILC subgroup) were comparable to those observed in the overall MONALEESA-3 population. Conclusions: Similar to the overall MONALEESA-3 population, RIB + FUL tx demonstrated an improvement in PFS and OS over PBO + FUL in patients with ILC, including among those treated in the 1L setting. The efficacy benefit of RIB observed in patients with HR+/HER2- ABC with the ILC subtype, including those receiving 1L tx, further supports the use of RIB in this patient population. Citation Format: M. De Laurentiis, J. Mouabbi, S. Im, M. Kruse, S. Chia, S. Brucker, C. Villanueva, G. Jerusalem, M. Gao, G. Sopher, J. Wu, J. Zarate, J. Beck. Progression-free survival (PFS) and overall survival (OS) results from the phase 3 MONALEESA-3 trial of postmenopausal patients with hormone receptor-positive (HR+)/HER2-negative (HER2−) advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL): A subgroup analysis of patients with invasive lobular carcinoma (ILC) [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 PS1-10-27.