Chicago, IL—The addition of the cyclin-dependent kinase (CDK)4/CDK6 inhibitor ribociclib to standard endocrine therapy significantly extended overall survival (OS) compared with endocrine therapy alone in premenopausal women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, according to results of the phase 3 MONALEESA-7 clinical trial, presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.
MONALEESA-7 is the first study to demonstrate significantly longer OS in patients who received a CDK4/CDK6 inhibitor plus endocrine therapy combination versus endocrine therapy alone as initial therapy for advanced breast cancer, and likely represents a new standard of care in this population.
“This is the first study to show improvement for any targeted therapy when used with first-line [endocrine therapy] for advanced breast cancer. MONALEESA-7 was the first phase 3 trial with a CDK4/6 inhibitor [conducted] exclusively in premenopausal patients, and use of ribociclib as front-line therapy significantly prolonged survival, which is good news for women with this terrible disease,” said lead investigator Sara A. Hurvitz, MD, Medical Oncologist, Jonsson Comprehensive Cancer Center, University of California, Los Angeles.
ASCO Expert Harold J. Burstein, MD, PhD, Associate Professor of Medicine, Harvard University, Cambridge, MA, and Medical Oncologist, Dana-Farber Cancer Institute and Brigham & Women’s Hospital, Boston, commented on this study at a press conference. “Advanced breast cancer in premenopausal women can be very aggressive. It is important and encouraging to see a targeted therapy that significantly increases survival for younger women.”
Ribociclib is approved by the US Food and Drug Administration in combination with an aromatase inhibitor for the treatment of pre- and perimenopausal women with HR-positive, HER2-negative advanced breast cancer.
The MONALEESA-7 trial randomized 672 premenopausal women with HR-positive, HER2-negative advanced breast cancer to goserelin (Zoladex) plus either ribociclib (N = 335) or placebo (N = 337). All participants also received either a nonsteroidal aromatase inhibitor or tamoxifen.
Median follow-up was 34.6 months. At interim analysis data cutoff (November 2018), treatment was ongoing in 35% of patients in the ribociclib arm and 17% of patients in the placebo arm. Dr Hurvitz said the majority of patients who ended treatment had disease progression.
Patients receiving ribociclib plus endocrine therapy had a significantly longer median OS than patients receiving placebo plus endocrine therapy (not reached vs 40.9 months; P = .00973). OS analysis showed that “there was a 29% relative reduction in risk of death [in patients in the ribociclib arm],” Dr Hurvitz said. A consistent OS benefit was observed across all subgroups.
After 42 months of treatment, 70.2% of women in the ribociclib arm were alive versus 46% of those in the placebo arm.
Median progression-free survival (PFS) was 23.8 months in the ribociclib arm versus 13 months in the placebo arm.
“The benefit of ribociclib extended beyond the initial treatment based on the time-to-subsequent chemotherapy and PFS2,” said Dr Hurvitz. PFS2 was defined as time from random selection to progression on the next line of therapy or death. The rate of PFS2 was significantly higher with ribociclib (P = .00973).
After 15 months of follow-up, adverse events in the ribociclib arm remained consistent with the drug’s known safety profile. Grade 3 or 4 events of special interest in the ribociclib and placebo arms were neutropenia (63.5% ribociclib vs 4.5% placebo), hepatobiliary toxicity (11.0% ribociclib vs 6.8% placebo), and prolonged QT interval (1.8% ribociclib vs 1.2% placebo).
Formal discussant Angelo Di Leo, MD, PhD, Department Head, Sandro Pitigliani Medical Oncology Unit, and Chair, Oncology Department, Hospital Prato, Istituto Toscano Tumori, Italy, said, “The MONALEESA-7 results are now setting a new standard of care for patients who are endocrine-therapy naïve. I think that this is now a population where we should consider combination of a CDK4/6 inhibitor plus endocrine therapy as a new standard of care.”
“My personal opinion is that this result should be expanded also to the menopausal population. The endocrine-sensitive population is the population who relapsed after at least 1 year from the end of adjuvant endocrine therapy,” Dr Di Leo added.