Topline results from the MONALESSA-7 trial showed that ribociclib (Kisqali) met its primary endpoint for progression-free survival (PFS) in premenopausal women with hormone-receptor (HR)–positive, HER2-negative (HR+/HER2-) advanced or metastatic breast cancer.
Novartis announced the finding in a press release, but did not provide any other details. The company plans to present the full results next month at the 40th Annual San Antonio Breast Cancer Symposium (SABCS). The company said MONALEESA-7 is the first prospective global phase III trial in more than 20 years designed specifically for premenopausal women diagnosed with advanced breast cancer to demonstrate superiority of any CDK4/6 inhibitor in combination with oral hormonal therapies and goserelin compared with endocrine treatment alone.
“There remains a significant unmet treatment need in younger women diagnosed with premenopausal advanced breast cancer, as the disease tends to be more aggressive with a poorer prognosis,” said Samit Hirawat, executive vice president and head, Global Drug Development, Novartis Oncology. “The MONALEESA-7 trial is the first CDK 4/6 inhibitor Phase III trial designed specifically for this patient population, and we are excited that the study met its primary endpoint, which may allow us to expand the population of patients who can benefit from treatment with Kisqali.”
MONALEESA-7 is a randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of ribociclib in combination with oral hormonal therapies and goserelin versus endocrine treatment alone in premenopausal or perimenopausal women with HR+/HER2- advanced breast cancer who had not previously received endocrine therapy for advanced disease.
In August, the European Commission (EC) approved the CDK 4/6 inhibitor for use in combination with an aromatase inhibitor for the frontline treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer.
The approval is based on the phase III MONALEESA-2 trial, in which frontline treatment with ribociclib plus letrozole (Femara) improved PFS by 9.3 months compared with letrozole plus placebo.
After a median follow-up of 26.4 months, the median PFS was 16.0 months (95% CI, 13.4-18.2) with letrozole plus placebo compared with 25.3 months (95% CI, 23.0-30.3) for ribociclib and letrozole, representing a 43% reduction in the risk of progression or death with the addition of the CDK4/6 inhibitor (HR, 0.568; 95% CI, 0.457-0.704; P
<.0001). The 24-month PFS rate was 54.7% with ribociclib versus 35.9% for placebo.
The frontline ribociclib approval is applicable to all 28 European Union member states plus Iceland, Norway, and Liechtenstein.
In the phase III study, 668 postmenopausal women with advanced breast cancer were randomized to letrozole plus ribociclib (n = 334) or placebo (n = 334). Letrozole was administered at 2.5 mg per day and ribociclib was given at 600 mg per day for 3 weeks followed by 1 week off.
The benefits of ribociclib were consistent across patient subgroups for PFS. For those in the United States, the median PFS was 27.6 months with the ribociclib combination versus 15 months with placebo (HR, 0.527; 95% CI, 0.351-0.793). The reduction in the risk of progression or death with ribociclib versus placebo was also consistent for those with ECOG performance status 0 (42% reduction) and 1 (46% reduction) and for those above 65 years of age (34%) and those below 65 years (48%).
The objective response rate with ribociclib was 42.5% versus 28.7% with placebo. The response to ribociclib included a complete response (CR) rate of 3.9% and a partial response (PR) rate of 38.6%. In the placebo arm, 2.4% and 26.3% had a CR and PR, respectively. Overall, 26.9% and 32% of patients had stable disease in the ribociclib and placebo arms, respectively.
At the time of the analysis in January 2017, overall survival (OS) data remained immature. Based on 15% of events in the CDK4/6 inhibitor arm and 19.8% in the placebo group, there was an early 25% reduction in the risk of death observed with ribociclib, which was not statistically significant (HR, 0.746; 95% CI, 0.517-1.078; P
= .059). The 24-month OS rate was 86.7% with ribociclib and 84.8% with placebo.
After 26.4 months of follow-up, 39.2% of patients continued to receive treatment with ribociclib and 26.3% continued in the placebo group. The most common cause for treatment discontinuation was disease progression (39.8% with ribociclib versus 60.8% with placebo). Adverse events (AEs) resulted in discontinuation for 8.1% of those in the ribociclib arm versus 2.4% of those in the placebo group.