MONALEESA Data Reveal Robust Long-Term Disease Control With Ribociclib

A pooled analysis of phase 3 MONALEESA trial data shows that first-line ribociclib (Kisqali; Novartis) continues to deliver clinically meaningful survival benefits for patients with hormone receptor–positive, HER2-negative (HR+/HER2–) advanced breast cancer (ABC). Presented at the San Antonio Breast Cancer Symposium, these findings reinforce ribociclib’s position as a foundational first-line therapy in this patient population.

Ribociclib in HR+, HER2- Breast Cancer

Ribociclib is a selective CDK4/6 inhibitor that blocks CDK4 and CDK6 proteins to halt cell cycle progression and suppress tumor growth. The therapy first received FDA approval in 2017 in combination with an aromatase inhibitor for postmenopausal women with HR+/HER2– advanced or metastatic breast cancer, based on the pivotal MONALEESA-2 trial (NCT01958021). Its indication expanded in 2018 to include additional HR+/HER2– advanced breast cancer populations, and in 2024 it gained approval in the adjuvant setting for individuals with high-risk stage 2 or 3 early breast cancer, including those with node-negative disease.^1,2

Ribociclib is administered orally once daily on a 3-weeks-on, 1-week-off schedule alongside an aromatase inhibitor, with the NATALEE trial (NCT03701334) supporting the tolerability of a 200-mg tablet regimen.^1,3

Across its clinical development program—which includes MONALEESA-2, MONALEESA-3 (NCT02422615), and MONALEESA-7 (NCT02278120)—ribociclib has consistently demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) when combined with endocrine therapy in both premenopausal and postmenopausal patients with HR+/HER2– ABC.^4,5

A Pooled Analysis of the MONALEESA Trials

Building on this foundation, investigators conducted a pooled exploratory analysis to better understand the durability of first-line ribociclib benefit across MONALEESA-2, -3, and -7. The analysis included premenopausal patients enrolled in MONALEESA-7 and postmenopausal patients from MONALEESA-2 and -3 who received ribociclib with endocrine therapy.⁶

To focus the evaluation on treatment-naïve advanced breast cancer, patients with early relapse—defined as a treatment-free interval of 12 months or less following (neo)adjuvant endocrine therapy—and those who received tamoxifen in MONALEESA-7 were excluded.

Long-term response (LTR) was defined as PFS longer than 4 years, a benchmark selected because the median PFS with first-line CDK4/6 inhibitors is approximately 2 years. Very long-term response (VLTR), assessed only in postmenopausal patients due to follow-up duration, was defined as PFS beyond 5 years.⁶

Across the MONALEESA studies, the median follow-up was 6.1 years (6.7 years in MONALEESA-2, 5.9 years in MONALEESA-3, and 4.5 years in MONALEESA-7).⁶

Findings

Among the 666 patients treated with first-line ribociclib plus endocrine therapy, 109 remained on treatment at data cutoff. In total, 153 patients (23.0%) achieved an LTR, and an additional 164 patients (24.6%) were censored before reaching the 4-year benchmark. Patients who achieved LTR had a median PFS of 6.8 years (95% CI, 6.4 years–not estimable) and a median OS that was not estimable (95% CI, 7 years–not estimable), indicating ongoing survival benefit at the time of analysis.⁶

LTR rates were comparable in premenopausal (22.7%) and postmenopausal (23.1%) patients. However, patients with LTR were less likely to present with high-risk disease features such as liver metastases (16.3% vs 25.5%) or three or more metastatic sites (30.1% vs 43.0%). Bone-only disease occurred at similar rates across groups.⁶

Molecular analyses provided additional insight into factors associated with long-term response. Patients achieving LTR had lower mean circulating tumor DNA (ctDNA) fractions at baseline and were less likely to harbor CCND1 or TP53 alterations. They also demonstrated lower baseline expression of CCNE1 and a higher prevalence of luminal A subtype disease based on PAM50 profiling.⁶

Among postmenopausal patients, 88 individuals (17.1%) met the criteria for VLTR, with further subgroup findings to be presented separately.⁶

These findings indicate that approximately 1 in 4 patients receiving first-line ribociclib may achieve disease control lasting more than 4 years—far exceeding the typical PFS seen with targeted therapy in HR+/HER2– ABC. This reinforces ribociclib’s role in delivering substantial and lasting clinical benefit for a wide range of patients.

REFERENCES

1. Gerlach A. Five-year NATALEE data show ribociclib improves outcomes in high-risk HR+/HER2– early breast cancer. Pharmacy Times. October 17, 2025. Accessed December 8, 2025. https://www.pharmacytimes.com/view/five-year-natalee-data-show-ribociclib-improves-outcomes-in-high-risk-hr-her2-early-breast-cancer

2. Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer (MONALEESA-2). Clinicaltrials.gov. Updated March 7, 2025. Accessed December 8, 2025. https://clinicaltrials.gov/study/NCT01958021

3. A trial to evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/​HER2- early breast cancer (NATALEE). Clinicaltrials.gov. Updated October 21, 2025. Accessed December 8, 2025. https://clinicaltrials.gov/study/NCT03701334

4. 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 8, 2025. https://clinicaltrials.gov/study/NCT02422615

5. Study of efficacy and safety in premenopausal women with hormone receptor positive, HER2-negative advanced breast cancer (MONALEESA-7). Clinicaltrials.gov. Updated March 12, 2024. Accessed December 8, 2025. https://clinicaltrials.gov/study/NCT02278120

6. Andre F, Fasching PA, Prat A, et al. 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). Presented at: 2025 San Antonio Breast Cancer Symposium. December 9-12, 2025. San Antonio, TX. Abstract PD5-10