Endocrine therapy plus ribociclib yields overall survival advantage in HR+/HER2-negative breast cancer

Medical writer: Jasenka Piljac Žegarac, PhD

Significantly longer overall survival (OS) was observed in women treated with endocrine therapy (ET) plus ribociclib, compared with women treated with ET alone, in the phase III MONALEESA-7 trial of premenopausal women with HR+/HER2-negative advanced breast cancer (ABC). This is the first study demonstrating significantly longer OS in patients treated with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus ET combination, compared to ET alone, as initial endocrine-based therapy.

“MONALEESA-7 was the first phase III trial with a CDK4/6 inhibitor [conducted] exclusively in premenopausal patients,” said Sara A. Hurvitz, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Centre, on June 4 (Abstract LBA1008).

A total of 672 premenopausal women with HR+/HER2-negative ABC who had not received ET for metastatic disease or who had received up to one prior line of chemotherapy were randomly assigned 1:1 to either 600 mg/day ribociclib plus goserelin (335) or placebo plus goserelin (337), with either a nonsteroidal aromatase inhibitor (letrozole or anastrozole) or tamoxifen. All women were younger than age 59, and the average age in both arms was comparable (age 43 years in the ribociclib plus ET arm and age 45 years in the placebo plus ET arm). The dosing regimen was 3 weeks on, followed by 1 week off treatment.

“The primary endpoint was progression-free survival (PFS), locally assessed, and our key secondary endpoint was OS,” Dr. Hurvitz said. OS was assessed using the Kaplan-Meier method and was compared by a one-sided stratified log-rank test, with superior efficacy defined as p ≤ 0.01018.

Median follow-up was 34.6 months. At interim analysis data cut off (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 did so because of disease progression.

Patients receiving ribociclib plus ET had a significantly longer median OS than patients receiving placebo plus ET (not reached vs. 40.9 months, 95% CI [37.80 months, not evaluable]; HR = 0.712 95% CI [0.54, 0.95]; P = 0.00973). OS analysis showed that “there was a 29% relative reduction in risk of death [in patients in the ribociclib arm],” Dr. Hurvitz said. “The median OS was not met in the ribociclib arm and was 40.9 months in the placebo arm,” she said. She added that “there was a consistent OS benefit seen across the subgroups.”

According to Dr. Hurvitz, “The benefit of ribociclib extended beyond the initial treatment based on the time-to-subsequent chemotherapy and PFS-2.” PFS-2 was defined as time from random selection to progression on the next line of therapy or death. The prespecified stopping boundary for superior efficacy was reached, with a p value of 0.00973.

In presenting safety data, Dr. Hurvitz noted that after 15 months of follow up, the adverse event profile for the ribociclib arm remained consistent with the known safety profile. Grade 3/4 events of special interest in the ribociclib and placebo arms were neutropenia (63.5% ribociclib and 4.5% placebo), hepatobiliary toxicity (11.0% ribociclib and 6.8% placebo), and prolonged QT interval (1.8% ribociclib and 1.2% placebo).

In the discussion that followed, Angelo Di Leo, MD, PhD, of the Hospital of Prato, Instituto Toscano Tumouri, Italy, said that the “MONALEESA-7 results are now setting a new standard of care for patients who are endocrine-therapy naive. 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,” he continued, and he noted that the “endocrine-sensitive population is the population who relapsed after at least 1 year from the end of adjuvant endocrine therapy.”

 

Featured video: Phase III MONALEESA-7 trial of premenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy ± ribociclib: Overall survival (OS) results.

 



Posted on 15 July 201925 March 2021