Ribociclib was found to prolong overall survival and improve post-progression outcomes in patients with HR-positive/HER2−negative advanced breast cancer, particularly among younger patients with a significant unmet need.
In the phase 3 MONALEESA-7 trial assessing the efficacy of the endocrine therapy (ET) ribociclib (Kisqali; Novartis Pharmaceuticals) in premenopausal patients with human epidermal growth factor receptor-2-negative (HR-positive/HER2−negative) advanced breast cancer (ABC), ribociclib was found to prolong overall survival (OS) and improve post-progression outcomes in patients with HR-positive/HER2−negative ABC, particularly among younger patients with a significant unmet need.
The multi-center, randomized, double-blinded, placebo controlled MONALEESA-7 trial assessed the efficacy of ribociclib, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), based on progression free survival (PFS).
In the trial, investigators observed that ribociclib and ET significantly prolonged OS among pre- or perimenopausal patients with HR-positive/HER2−negative ABC at a median of 58.7 months, while patients treated with the placebo and ET had a median OS of 48.0 months (HR, 0.76 [95% CI, 0.61-0.96]).
Additionally, due to the separation of patients by age subgroups, the investigators found that younger patients with HR-positive/HER2−negative ABC had a poorer prognosis. This was assessed by conducting an exploratory analysis that characterized outcomes in patients under 40 years of age versus those over 40 years of age.
Investigators structured the trial by randomizing pre- or perimenopausal patients with HR-positive/HER2−negative ABC with no prior CDK4/6i or ET for ABC 1:1 to receive ribociclib or placebo plus goserelin and a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen. To assess OS and other efficacy endpoints, investigators also used the Cox proportional hazards model and summarized the results using Kaplan-Meier methods.
With a data cutoff point of June 29, 2020, the median follow-up time was 53.5 months. In the ribociclib versus placebo arm, 98 versus 88 patients were under 40 years of age and 237 versus 249 patients were 40 years of age or older.
In patients aged younger than 40 years, the median age in the ribociclib arm was 35 years versus 36 years in the placebo arm, with a range between 25 and 39 years of age and between 29 and 39 years of age, respectively.
Among patients 40 years of age or older, the median age of patients in the ribociclib arm was 45 years versus 46 years in the placebo arm, with a range between 40 and 58 years and between 40 years and 58 years, respectively.
In patients under 40 years of age, the investigators found that ribociclib and ET demonstrated an OS benefit versus placebo and ET, at a median of 51.3 months versus 40.5 months (HR, 0.65; 95% CI, 0.43-0.98). Among patients 40 years of age or older, ribociclib had a longer median OS versus placebo, with a median of 58.8 months versus 51.7 months (HR, 0.81; 95% CI, 0.62-1.07).
Investigators observed similar trends in OS among NSAI-treated patients, as well as among all patients for the second progression-free survival (PFS2), time to chemotherapy (CT), and CT-free survival (Table).
Among patients who discontinued treatment, 77.3% versus 75.0% of patients under 40 years of age received subsequent antineoplastic therapies in the ribociclib arm versus placebo arm, respectively, whereas 77.2% versus 79.2% of patients received subsequent therapies among those 40 years of age or older.
Additionally, subsequent CDK4/6i were received among 16.0% versus 27.5% of patients younger than 40 years of age, whereas among patients 40 years of age or older, it was 11.6% versus 25.7% in the ribociclib versus the placebo arms. Regarding adverse events, investigators found that they were consistent with the known safety profile observed in the MONALEESA-7 trial.
Data obtained from trial results published in Annals of Oncology.
Lu YS, El Saghir NS, Hurvitz SA, et al. 93MO Overall survival (OS) results by age subgroup from the phase III MONALEESA-7 (ML-7) trial of premenopausal patients (pts) with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Annals of Oncology. 2021;32(2):S62. doi: 10.1016/j.annonc.2021.03.107.