Overall Survival With the Addition of Ribociclib to Endocrine Therapy in Advanced HR-Positive, HER2-Negative Breast Cancer


Key Points

  • The addition of ribociclib to endocrine therapy resulted in significantly improved overall survival.
  • A significant survival benefit was observed among the subgroup of patients receiving nonsteroidal aromatase inhibitors.

As reported in The New England Journal of Medicine by Im et al, an interim analysis of the phase III MONALEESA-7 trial has shown an overall survival benefit with the addition of the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor ribociclib to endocrine therapy in pre- or perimenopausal women with advanced hormone receptor (HR)-positive, HER2-negative breast cancer. 

A prior report from the trial showed that the addition of ribociclib to endocrine therapy significantly improved progression-free survival, the primary endpoint of the trial.

Study Details

The double-blind trial included 672 women aged 18 to 59 years from 188 sites in 30 countries. They were randomly assigned between December 2014 and August 2016 to receive ribociclib at 600 mg daily for 21 consecutive days followed by 7 days off in 28-day cycles (n = 335) or matching placebo (n = 337).

Both groups received goserelin at 3.6 mg subcutaneously on day 1 of each 28-day cycle and either a nonsteroidal aromatase inhibitor (letrozole at 2.5 mg or anastrozole at 1 mg) or tamoxifen at 20 mg continuously once daily. Crossover between groups was not permitted. Patients had to have locoregionally recurrent or metastatic disease not amenable to curative therapy.

In the previously reported primary analysis, with a median follow-up of 19.2 months, median progression-free survival was 23.8 months in the ribociclib group vs 13.0 months in the placebo group (hazard ratio [HR] = 0.55, P < .0001).

Overall Survival

The second prespecified interim analysis of overall survival—the key secondary endpoint of the trial—was conducted after 192 patients had died, including 83 (24.8%) in the ribociclib group and 109 (32.3%) in the placebo group. Median duration of follow-up was 34.6 months. The Kaplan–Meier estimated overall survival at 42 months was 70.2% in the ribociclib group vs 46.0% in the placebo group (HR = 0.71, P = 0.00973), with the P value crossing the prespecified stopping boundary (P = .01018) for superiority of ribociclib.

Median overall survival could not be estimated in the ribociclib group vs 40.9 months in the placebo group (95% confidence interval [CI] = 37.8–could not be estimated). Estimated overall survival was 82.7% vs 81.8% at 24 months, and 71.9% vs 64.9% at 36 months.

Survival in Subgroups

Among the 495 patients who received an aromatase inhibitor (248 in the ribociclib group, 247 in the placebo group), median overall survival could not be estimated in the ribociclib group vs 40.7 months in the placebo group. Estimated overall survival at 42 months was 69.7% vs 43.0% (HR =  0.70,  95% CI = 0.50–0.98).

Among 177 patients who received tamoxifen (87 in the ribociclib group, 90 in the placebo group), median overall survival could not be estimated in either group. Estimated survival at 42 months was 71.2% vs 54.5% (HR = 0.79, 95% CI = 0.45–1.38).

Hazard ratios for overall survival favored ribociclib in most subgroups examined in exploratory analysis. Among 198 Asian patients, the hazard ratio was 0.40 (95% CI = 0.22–0.72), and among 413 non-Asian patients, the hazard ratio was 0.91 (95% CI = 0.64–1.30).

Subsequent Treatment

A total of 219 patients in the ribociclib group and 280 patients in the placebo group discontinued the study regimen. Among these, 68.9% vs 73.2% received subsequent therapy, most commonly chemotherapy alone (22.4% vs 28.6%) and hormone therapy alone (22.4% vs 20.4%).

At 42 months, 65.8% of the total ribociclib group vs 49.0% of the total placebo group had not yet received a first subsequent chemotherapy (HR = 0.60, 95% CI = 0.46–0.77). For progression-free survival during receipt of subsequent treatment, the estimated percentages of patients who were alive without progression at 42 months while receiving second-line therapy were 54.6% vs 37.8% (HR = 0.69, 95% CI = 0.55–0.87).

Adverse Events

Adverse events in the two groups in the current overall survival analysis were consistent with those reported in the primary analysis. Grade 3 or 4 adverse events of special interest were neutropenia, which occurred in 63.5% of the ribociclib group vs 4.5% of the placebo group. Hepatobiliary toxic effects, which occurred in 11.0% vs 6.8%; and prolonged QT interval, which occurred in 1.8% vs 1.2%.

The investigators concluded, “This trial showed significantly longer overall survival with a CDK4/6 inhibitor plus endocrine therapy than with endocrine therapy alone among patients with advanced hormone-receptor–positive, HER2-negative breast cancer. No new concerns regarding toxic effects emerged with longer follow-up.”

Disclosure: The study was funded by Novartis. For full disclosures of the study authors, visit


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