Practical Implications of the MONALEESA-3 Trial


Komal Jhaveri, MD, FACP:The MONALEESA-3 trial [was] a randomized phase III trial that actually evaluated the combination of fulvestrant with one of the CDK4/6 inhibitors—in this case…ribociclib with placebo for postmenopausal women. About 500 patients were then randomized to receiving the fulvestrant plus ribociclib combination, compared [with] ribociclib with placebo, with a primary endpoint of progression-free survival.

What was unique about this trial, compared [with] the PALOMA-3 trial or the MONARCH-2 trial that also evaluated the combination of fulvestrant with another CDK4/6 inhibitor—such as palbociclib in PALOMA-3 and abemaciclib in MONARCH-2—was that in the MONALEESA-3 trial, women could get fulvestrant with ribociclib even if they were treatment naive. Meaning, this could be a first-line therapy. And what was seen, in terms of their efficacy, was that the combination of fulvestrant with ribociclib led to a progression-free survival at about 20.5 months compared [with] 12.8 months in the group that had received fulvestrant plus placebo alone, with a hazard ratio of 0.59, which is statistically significant. So certainly, this data suggests that fulvestrant for the CDK4/6 inhibitor could be used as a first- or second-line treatment regimen for patients with [estrogen receptor]-positive metastatic disease.

This combination of fulvestrant with ribociclib could be an appropriate treatment approach. But our patient was 65 [and] postmenopausal, a de novo metastatic patient with disease in the bone, and she could certainly be treated with a fulvestrant with ribociclib-like agent based on the MONALEESA-3 trial, or an aromatase inhibitor with CDK4/6 inhibitor based on the other trials that have justified its use in the first-line setting.

The phase III PALOMA-3 trial evaluated the combination of fulvestrant with palbociclib, and similarly, the MONARCH-2 trial evaluated the combination of fulvestrant with abemaciclib. And these were all patients who had even progressed on their adjuvant therapy, or they had progressed in the metastatic setting after being treated with a nonsteroidal aromatase inhibitor in the first-line setting. So predominantly these were women who were treated with this combination in the second-line setting.

And what the trial showed, [what] both of these trials showed, [was] that the combination of the CDK4/6 inhibitor with fulvestrant led to a statistical improvement in progression-free survival compared [with] placebo with fulvestrant, making it a very valid second-line therapy option. So this is how we utilize fulvestrant in the first- or second-line setting.

Transcript edited for clarity.

A 65-Year-Old Woman With Metastatic ER+/PR+ Breast Cancer

December 2013

  • A 65-year-old woman was examined by her gynecologist after discovering a right-sided lump in her upper inner breast; she reported feeling exhausted lately, requiring frequent rest
  • PE showed a grape-sized right palpable mass at 3 o’clock
  • Diagnostic ultrasound showed a spiculated and hypoechoic mass measuring 26 x 23 x 21 mm; imaging in the left breast was unremarkable
  • Core biopsy showed high-grade infiltrating ductal carcinoma
    • Hormone receptor status: ER+/ PR+
    • HER2,IHC 1+
  • She underwent lumpectomy and axillary lymph node dissection that revealed a 2.3-cm infiltrating ductal carcinoma, 4 of 12 nodes were positive for disease
  • CT of the chest, abdomen, and pelvis showed that the disease had spread to her bones and biopsy confirmed metastatic disease
  • ECOG 1
  • She was started on ribociclib + fulvestrant
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