Ribociclib Efficacious in Patients with Unresectable or HR-Positive/HER2-Negative Metastatic Breast Cancer Receiving Fulvestrant or Exemestane After Not Responding to Prior Treatments

CDK4/6 inhibitors have been shown to improve PFS and overall survival (OS) in patients with HR-positive/HER2-negative metastatic breast cancer when coadministered with ET. Observational data suggest that continuing CDK4/6 inhibitor therapy and switching ET at progression may be beneficial, but no studies have been conducted to validate this until the MAINTAIN trial.

Men and women with measurable or nonmeasurable HR-positive/HER2-negative metastatic breast cancer whose cancer progressed during CDK4/6 inhibitor and ET were randomized 1:1 to fulvestrant or exemestane with or without ribociclib. Patients who had previously received fulvestrant received exemestane as the ET, and those who had previously received exemestane received fulvestrant; in those who had previously received neither fulvestrant nor exemestane, choice of the ET was at the investigator’s discretion, although fulvestrant was prioritized. The primary outcome was PFS. With a sample size of 120 randomized and evaluable patients and a significance level alpha of 2.5%, a 1-sided log-rank test had 80% power to detect an effect size (difference in PFS) of 3 months.

One patient was removed from the study for failing to take ET with ribociclib/placebo. Only 1 patient was male; the median age was 57.0 years; 88 (74%) patients were white and 21 (17.6%) were Hispanic. In terms of ET, 99 (83%) patients were given fulvestrant and 20 (17%) patients were given exemestane. In terms of prior therapy with a CDK4/6 inhibitor, 100 (87%) patients had received palbociclib, 13 (11%) patients had ribociclib, 2 (2%) patients had abemaciclib, and 4 (3%) patients received palbociclib plus another CDK4/6 inhibitor.

A significant benefit in median PFS was seen in patients who were randomized to fulvestrant or exemestane plus ribociclib (5.33 months; 95% confidence interval [CI], 3.25-8.12) versus placebo (2.76 months; 95% CI, 2.66-3.25), a difference associated with a hazard ratio of 0.56 (95% CI, 0.37-0.83; P = .004). In the subset of patients treated with fulvestrant, similar results were obtained: median PFS of 5.29 months for those assigned to ribociclib versus placebo (2.76 months; hazard ratio, 0.59; 95% CI, 0.38-0.91; P = .02). At 6 months, PFS was 42% in the ribociclib arm, compared with 24% of those in the placebo arm. At 12 months, PFS was 25% in the ribociclib arm, compared with 7% in the placebo arm.

In conclusion, addition of ribociclib plus switching ET following progression on prior CDK4/6 inhibitor therapy resulted in a substantial and clinically meaningful PFS advantage for patients with HR-positive/HER2-negative metastatic breast cancer in this randomized, placebo-controlled phase 2 study.


Kalinsky K, Accordino MK, Chiuzan C, et al. A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial. J Clin Oncol. 2022;40:17. Abstract LBA1004.

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