119 Progression-Free Survival (PFS) and Overall Survival (OS) Results From the Phase 3 MONALEESA-3 Trial of Postmenopausal Patients With Hormone Receptor–Positive (HR+)/Human Epidermal Growth Factor Receptor 2–Negative (HER2−) Advanced Breast Cancer (ABC) Treated With Ribociclib (RIB) + Fulvestrant (FUL): A Subgroup Analysis of Patients With Invasive Lobular Carcinoma (ILC)

Background

MONALEESA-3 reported statistically significant overall survival (OS) benefits with ribociclib plus fulvestrant, which were maintained with extended follow-up. Patients with invasive lobular carcinoma (ILC) subtype, 10% to 15% of breast cancer cases, show unique clinicopathological characteristics. This exploratory analysis examined progression-free survival (PFS), OS, response rates, and safety in patients with ILC in MONALEESA-3, including those receiving first-line treatment.

Methods

Postmenopausal patients with hormone receptor–positive/HER2-negative advanced breast cancer were randomly assigned 2:1 to receive first-line/second-line ribociclib plus fulvestrant or placebo plus fulvestrant. PFS and OS were stratified by lung/liver metastasis and previous endocrine therapy. Data cutoff for this analysis was January 11, 2023. This was a descriptive analysis of the subgroup of patients with ILC.

Results

Of all MONALEESA-3 patients (N = 726), 120 (16.5%) had ILC, (ribociclib, n = 77; placebo, n = 43). 83.3% of patients had bone metastasis (ribociclib, 81.8%; placebo, 86.0%), and 45.0% had visceral metastasis (ribociclib, 48.1%; placebo, 39.5%). Of 354 patients receiving first-line treatment, 56 (15.8%) had ILC subtype (ribociclib, n = 38;placebo, n = 18); 17.5% of patients had de novo advanced breast cancer (ribociclib, 18.2%; placebo, 16.3%), and 81.7% experienced relapse more than 12 months after initial diagnosis (ribociclib, 80.5%; placebo, 83.7%). Baseline characteristics were similar in patients with ILC receiving first-line treatment. Patients with ILC receiving ribociclib plus fulvestrant had longer PFS (median, 20.5 months) than those receiving placebo plus fulvestrant (median, 9.4 months; HR, 0.56; 95% CI: 0.37-0.86). Median PFS was also prolonged in patients with ILC receiving first-line ribociclib plus fulvestrant (median, 26.3 months) over first-line placebo plus fulvestrant (median, 18.1 months; HR, 0.78; 95% CI: 0.39-1.59). Patients with ILC receiving ribociclib plus fulvestrant had longer OS (median, 51.2 months) vs placebo plus fulvestrant (median, 30.8 months; HR, 0.62; 95% CI: 0.39-0.98); median OS in patients with ILC receiving first-line ribociclib plus fulvestrant vs placebo plus fulvestrant was 59.6 vs 40.0 months, respectively (HR, 0.54; 95% CI: 0.25-1.19). Rates of adverse events in the ribociclib arm in the ILC subgroup were comparable with the overall MONALEESA-3 population.

Conclusions

Similar to the overall MONALEESA-3 population, ribociclib plus fulvestrant demonstrated an improvement in PFS and OS over placebo plus fulvestrant in patients with ILC, including those treated in the first-line setting. This efficacy benefit of ribociclib in patients with hormone receptor–positive/HER2-negative advanced breast cancer with the ILC subtype, including those receiving first-line treatment, further supports the use of ribociclib in this patient population.

Previously presented at 2025 SABCS: De Laurentiis M, et al. December 9-12, 2025; San Antonio, TX. Poster PS1-10-27. Reused with permission.