Ribociclib Plus Fulvestrant Shows Strong PFS and OS Benefits in Patients With Invasive Lobular Carcinoma

Exploratory findings from the phase 3 MONALEESA-3 trial (NCT02422615) highlight the benefit of ribociclib (Kisqali; Novartis) plus fulvestrant (Faslodex; AstraZeneca) for patients with hormone receptor–positive, HER2-negative (HR+/HER2–) advanced breast cancer who have invasive lobular carcinoma (ILC), a distinct histologic subtype that accounts for 10% to 15% of breast cancer cases.^1,2

The results, presented at the 2025 San Antonio Breast Cancer Symposium in San Antonio, Texas, reinforce the role of ribociclib-based endocrine therapy in improving progression-free and overall survival in this population.

Ribociclib Improves Survival in MONALEESA-3

The original MONALEESA-3 study demonstrated a significant survival advantage for ribociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal patients receiving first-line (1L) or second-line (2L) treatment. At the primary analysis, median progression-free survival (PFS) improved from 12.8 months in the placebo arm to 20.5 months with ribociclib (HR, 0.59), and a statistically significant overall survival (OS) benefit emerged at the final analysis (HR, 0.72). With longer follow-up beyond 56 months, this OS benefit remained durable.²

Given the unique biology, metastatic patterns, and treatment responses associated with ILC, investigators conducted a subgroup analysis to better understand outcomes among these patients within MONALEESA-3.²

Study Design and ILC Subgroup Characteristics

Among the 726 patients enrolled, 120 (16.5%) had ILC, with 77 randomized to ribociclib plus fulvestrant and 43 to placebo plus fulvestrant. The subgroup mirrored the broader study population, with a median age of 63 years and balanced baseline characteristics across treatment arms. Most patients (more than 80%) had relapsed over 12 months after completing prior adjuvant or neoadjuvant endocrine therapy, and a majority had bone metastases. Visceral metastases were present in about 45% of patients with ILC.²

A subset analysis examined outcomes specifically in the first-line setting, which included 56 patients with ILC.²

Improved PFS and OS With Ribociclib in the ILC Subgroup

Patients with ILC experienced a substantial PFS advantage with ribociclib. Median PFS was 20.5 months with ribociclib plus fulvestrant compared with 9.4 months with placebo plus fulvestrant (HR, 0.56). This improvement reflected nearly a doubling of disease control duration.²

In the 1L setting, patients with ILC receiving ribociclib plus fulvestrant showed an even longer median PFS of 26.3 months, compared with 18.1 months for those receiving placebo, although this comparison did not reach statistical significance given the small sample size (HR, 0.78).²

OS outcomes were similarly favorable. Median OS for patients with ILC treated with ribociclib plus fulvestrant reached 51.2 months, compared with 30.8 months for placebo (HR, 0.62). Among first-line patients, OS extended to 59.6 months with ribociclib versus 40.0 months with placebo.²

These findings indicate that the survival benefit seen in the overall MONALEESA-3 population is preserved—and potentially magnified—in patients with the ILC subtype.²

Safety Profile Consistent With Overall Trial Population

Ribociclib was well tolerated in the ILC subgroup. Rates of key adverse events, including neutropenia and liver enzyme elevations, were comparable to those observed in the overall trial population. No new safety signals emerged in the ILC cohort or the 1L subgroup.²

This exploratory analysis suggests that ribociclib plus fulvestrant provides meaningful PFS and OS benefits for patients with HR+/HER2– ILC, reinforcing its role as an important treatment option in both first- and second-line settings. As ILC continues to be recognized as a biologically and clinically distinct subtype, these data support the continued use of CDK4/6 inhibitors as foundational therapy for this patient population.

REFERENCES

1. Study of efficacy and safety of LEE011 in men and postmenopausal women with advanced breast cancer (MONALEESA-3). ClinicalTrials.gov. Updated November 30, 2023. Accessed December 12, 2025. https://clinicaltrials.gov/study/NCT02422615

2. De Laurentiis M, Mouabbi J, Im S, et al. 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). Presented at: SABCS 2025. December 9-12, 2025. Abstract PS1-10-27. Accessed December 12, 2025.