Chicago, IL—The addition of the cyclin-dependent kinase (CDK)4/CDK6 inhibitor ribociclib (Kisqali) 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 ASCO 2019.
MONALEESA-7 is the first study to demonstrate significantly prolonged OS in patients who receive treatment with the combination of a CDK4/CDK6 inhibitor and endocrine therapy versus endocrine therapy alone as an initial endocrine-based therapy for advanced breast cancer. This study’s results likely represent a new standard of care in this population, according to lead investigator Sara A. Hurvitz, MD, Medical Director, Clinical Research Unit, Jonsson Comprehensive Cancer Center, University of California, Los Angeles.
“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 Dr Hurvitz.
“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,” said ASCO Expert Harold J. Burstein, MD, PhD, FASCO, Institute Physician, Breast Oncology Program, Dana-Farber Cancer Institute, Boston, who commented on this study at a press conference at the meeting.
Ribociclib is indicated 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 clinical trial included 672 premenopausal women (aged <59 years) with HR-positive, HER2-negative advanced breast cancer who had not received endocrine therapy for metastatic disease or who had received up to 1 previous line of chemotherapy. The women were randomized in a 1:1 ratio to daily ribociclib (600 mg) plus goserelin (Zoladex; N = 335) to suppress estrogen or to placebo plus goserelin (N = 337), along with a nonsteroidal aromatase inhibitor—letrozole (Femara) or anastrozole (Arimidex)—or with tamoxifen.
The median follow-up was 34.6 months. At the interim analysis data cutoff in November 2018, treatment was ongoing in 35% of patients in the ribociclib arm and 17% of patients in the placebo arm. Dr Hurvitz said that 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—OS not reached versus 40.9 months (P = .00973). The OS analysis showed that “there was a 29% relative reduction in risk of death [in the ribociclib arm],” Dr Hurvitz said. A consistent OS benefit with ribociclib was observed across all subgroups.
After 42 months of treatment, 70.2% of women in the ribociclib arm were alive versus only 46% of those who received placebo.
The study met its primary end point of progression-free survival (PFS) with ribociclib plus endocrine therapy. The median PFS was 23.8 months in the ribociclib arm versus 13 months in the placebo arm (P <.0001).
According to Dr Hurvitz, “The benefit of ribociclib extended beyond the initial treatment, based on the time-to-subsequent chemotherapy and PFS2.” PFS2 is a relatively new term defined as time from random selection to disease progression during the next line of therapy or death. The rate of PFS2 was significantly greater with ribociclib versus placebo (P = .00973).
After 15 months of follow-up, the adverse event profile for the ribociclib arm remained consistent with the drug’s known safety profile. Grade 3 or 4 adverse events of special interest in the ribociclib and placebo arms were neutropenia (63.5% vs 4.5%, respectively), hepatobiliary toxicity (11.0% vs 6.8%, respectively), and prolonged QT interval (1.8% vs 1.2%, respectively).
“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 the combination of a CDK4/6 inhibitor plus endocrine therapy as a new standard of care,” said formal discussant Angelo Di Leo, MD, PhD, Sandro Pitigliani Medical Oncology Department, Hospital of Prato, Italy.
“My personal opinion is that this result should be expanded also to the menopausal population,” he continued. “The endocrine-sensitive population is the population who relapsed after at least 1 year from the end of adjuvant endocrine therapy.”