November 09, 2018
3 min read

Ribociclib-fulvestrant combination extends PFS for certain postmenopausal women with breast cancer

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NEW YORK — The addition of ribociclib to fulvestrant significantly improved PFS among women with hormone receptor-positive, HER2-negative advanced breast cancer, according to results of the MONALEESA-3 study presented at Chemotherapy Foundation Symposium.

The benefit of ribociclib (Kisqali, Novartis) — a CDK 4/6 inhibitor — appeared consistent across patient subgroups. In addition, the combination demonstrated a manageable safety profile that appeared consistent with prior phase 3 studies of ribociclib.

“This is the first study to show that CDK 4/6 inhibitor plus fulvestrant combinations are efficacious in patients with de novo advanced breast cancer, and in patients [who] relapsed more than 12 months after completion of neoadjuvant endocrine therapy,” Dennis J. Slamon, MD, PhD, director of clinical/translational research at UCLA Jonsson Comprehensive Cancer Center, and colleagues wrote.

Results of the phase 3 MONALEESA-2 and MONALEESA-7 trials showed the addition of ribociclib to endocrine therapy significantly improved PFS among pre-, peri- and postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer.

Prior studies showed the combination of CDK 4/6 inhibitors and fulvestrant benefitted patients with hormone receptor-positive breast cancer that progressed on previous endocrine therapy. However, no study had assessed the combination of a CDK 4/6 inhibitor and fulvestrant among patients with de novo hormone receptor-positive, HER2-negative advanced breast cancer, or for patients who relapsed more than a year after previous endocrine therapy who received no additional treatment for advanced disease.

In the phase 3 MONALEESA-3 trial, Slamon and colleagues evaluated the efficacy and safety of ribociclib plus fulvestrant among postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who either were treatment naive or who received one line of endocrine therapy in the advanced setting.

The analysis included 726 women. Researchers randomly assigned 484 of them to ribociclib 600 mg daily on a 3-weeks-on, 1-week-off schedule plus fulvestrant 500 mg. The other 242 women received placebo plus fulvestrant.

PFS served as the primary objective. Secondary endpoints included OS, overall response rate, clinical benefit rate and safety.

All patients had ECOG performance status of 0 or 1. None had received prior chemotherapy for advanced breast cancer, nor had they received fulvestrant or any CDK 4/6 inhibitor.

Median duration from randomization to data cutoff was 20.4 months. Median duration of treatment was 15.8 months for women assigned ribociclib and 12 months for those assigned placebo.

Results showed significantly improved PFS with ribociclib by investigator assessment (median, 20.5 months vs. 12.8 months; HR = 0.59; 95% CI, 0.48-0.73) and by blinded independent review (median, not reached vs. 10.9 months; HR = 0.49; 95% CI, 0.34-0.7).


Researchers observed the PFS benefit among patients who received no prior endocrine therapy (HR = 0.57; 95% CI, 0.41-0.8) and those who received one prior line (HR = 0.56; 95% CI, 0.42-0.74).

Subgroup analysis showed benefit with ribociclib for patients with liver or lung involvement, those who received prior tamoxifen and those who received prior aromatase inhibitor therapy.

ORR was higher among ribociclib-treated patients in the entire cohort (32.4% vs. 21.5%; P = .000912) and among patients with measurable disease (40.9% vs. 28.7%; P = .003).

OS data were immature at cutoff.

A higher percentage of ribociclib-treated patients required dose reductions due to adverse events (33.1% vs. 3.3%) or discontinued treatment due to adverse events (68.5% vs. 18.7%).

Ribociclib-treated patients experienced higher rates of neutropenia (all grade, 69.6% vs. 2.1%; grade 3/grade 4, 53.4% vs. 0%), leukopenia (all grade, 28.4% vs. 1.7%; grade 3/grade 4, 14.1% vs. 0%), anemia (all grade, 17.2% vs. 5.4%) and thrombocytopenia (all grade, 8.5% vs. 1.7%). Other adverse events that were more common in the ribociclib group included nausea (45.3% vs. 28.2%), diarrhea (29% vs. 20.3%) and vomiting (26.7% vs. 12.9%).

The FDA has approved ribociclib plus fulvestrant for the treatment of postmenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, either as initial endocrine-based therapy or for those whose disease progressed on endocrine therapy. – by Mark Leiser

For more information:

Slamon DJ, et al. Ribociclib plus fulvestrant in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from MONALEESA-3. Presented at: Chemotherapy Foundation Symposium; Nov. 7-9, 2018; New York.


Novartis sponsored this study.