Comparison of Progression-Free Survival from the MONALEESA and RIBANNA Trials in Patients with HR-Positive/HER2-Negative Advanced Breast Cancer

The standard first-line (1L) treatment for HR-positive/HER2-negative advanced breast cancer (ABC) is CDK4/6 inhibition in combination with an aromatase inhibitor, such as ribociclib in combination with fulvestrant. Across the MONALEESA trials, ribociclib plus endocrine therapy (ET) demonstrated a clinically meaningful benefit in overall survival regardless of menopause status, line of therapy, or combination partner. RIBANNA, a prospective, non-interventional study, gathered real-world evidence on the efficacy and safety of ribociclib plus ET versus ET monotherapy or chemotherapy (CT) in a 1L setting in a broader patient population than studied in the MONALEESA trials, comprising pre-, peri-, and postmenopausal patients with HR-positive/HER2-negative ABC.

A matched-pair analysis of 1L progression-free survival (PFS) data from ribociclib plus ET, ET, and CT cohorts using propensity score matching, and comparison of the 1L PFS outcomes of ribociclib plus ET across MONALEESA-like subgroups from RIBANNA identified based on inclusion and exclusion criteria of the MONALEESA trials, along with updated safety data, were presented.

Of 2581 patients enrolled in the study, 2163 received 1L ribociclib plus ET, 237 received ET, and 181 received CT. The duration of follow-up was 4.9, 4.8, and 4.7 years among the ribociclib plus ET, ET, and CT cohorts, respectively. Data were available for 2486 (96.3%) patients on 1L treatment, with discontinuation rates of 42.1%, 44.3%, and 65.2% in the ribociclib plus ET, ET, and CT cohorts, respectively. Of 2146 patients included in the full analysis, 1811 (81.8%), 192 (78.4%), and 143 (73.0%) patients were from the ribociclib plus ET, ET, and CT cohorts, respectively. The safety analysis set (N = 2369) included 1984 (89.7%), 217 (88.6%), and 168 (85.7%) patients from the ribociclib plus ET, ET, and CT cohorts, respectively.

In the MONALEESA-like subgroup analysis, the Kaplan-Meier (KM) estimate for PFS was 38.1 months, 21.9 months, 32.3 months, and 31.0 months in the MONALEESA-2–like, -3–like, -7–like, and “other” subgroups, respectively. Results from the MONALEESA-7–like subgroup should be interpreted with caution due to a smaller sample size. Propensity score matching–adjusted analyses consistently demonstrated prolonged PFS with ribociclib plus ET versus ET monotherapy or CT among patients with HR-positive/HER2-negative metastatic breast cancer in real-world clinical practice. However, adjusted KM curves for 1L PFS at later time points should be interpreted with caution due to smaller sample size.

The mean duration (SD) of drug exposure for 1L treatment was 615.8 (457.7) days in the ribociclib plus ET cohort, 630.4 (434.2) days in the ET cohort, and 509.7 (559.0) days in the CT cohort. The most common treatment-emergent adverse events (TEAEs) of all grades in the ribociclib plus ET arm were neutropenia (25.8%), nausea (25.1%), fatigue (24.1%), and leukopenia (19.8%); nausea and fatigue were the most common all-grade TEAEs in both the CT and ET arms.

Despite diverse population characteristics among patients receiving ribociclib plus ET in the real-world setting, the RIBANNA trial revealed PFS benefit in pre- and postmenopausal patients with HR-positive/HER2-negative ABC. The subgroup analysis of MONALEESA-like populations in RIBANNA confirms PFS benefit with ribociclib treatment (regardless of subset) by showing it falls within the PFS range observed in the MONALEESA trials; this benefit was seen in patients within the “other” subset as well. Ribociclib was well tolerated, with no new safety signals observed in the RIBANNA trial.

Source:

Jackisch C, Brucker C, Decker T, et al. RIBANNA 5th interim analysis: matched-pair analysis of progression-free survival (PFS) across treatment cohorts and comparison of frontline ribociclib + endocrine therapy PFS data from RIBANNA vs MONALEESA trials in HR+, HER2- ABC. San Antonio Breast Cancer Symposium 2022. Abstract P4-01-01.