A Case of Estrogen-Driven Metastatic Breast Cancer - Episode 3

CDK4/6 Plus Endocrine Therapy as First-Line Approach

November 26, 2018

Komal Jhaveri, MD, FACP:There are a few factors that we take into consideration when we’re trying to treat a patient in the first line with metastatic disease. And the most important question that we want to answer for a patient with[estrogen receptor] (ER)-positive disease is, when would you consider chemotherapy in the first-line setting?

So the rule of thumb, if you will, for an ER-positive metastatic patient would be that you would always want to give them endocrine therapy unless there is a visceral crisis. And with visceral crisis, I’m not talking about just presence of metastases. I’m referring to a patient with a significant disease burden. Somebody who is presenting with a lot of symptoms, with severe maladies that make you feel [as if] she would benefit with chemotherapy and not endocrine therapy. But otherwise, with every other woman who is not in visceral crisis, the first-line choice is always going to be endocrine therapy. So that’s the first factor that we keep in mind.

Outside of that, you want to make sure that they are truly ER-positive from their metastatic site and notHER2+ or triple negative, because that would perhaps change the way you treat this patient. You want to keep in mind their menopausal status. Because for a premenopausal woman, you’re thinking about adding ovarian suppression to endocrine therapy. You want to think about whether they have been treated for their breast cancer or are they presenting with de novo metastasis, as in this case with this woman who presented as such with de novo metastatic disease. Because those factors will drive the choice of therapy for a given woman.

Given that we now have at least four randomized phase III trials, one dedicated to premenopausal women with the MONALEESA-7 trial and three others, such as the PALOMA 2, the MONALEESA-2, and the MONARCH-3 trials, that showed that CDK4/6 inhibitors are effective when combined with endocrine therapy. And all these trials showed roughly a hazard ratio of about 0.5 with a statistically significant improvement in progression-free survival compared [with] endocrine therapy alone. My practice certainly has been to utilize the combination of the CDK4/6 inhibitor with endocrine therapy for first-line treatment, or even second-line if they [have] not received a CDK4/6 inhibitor in patients with ER+ metastatic disease. So I would absolutely consider that treatment for this given woman as well.

[For] the data that we have from these phase III trials, we try to identify if there was a particular subgroup that might benefit more, or might not benefit from this combination. In other words, [for the] biggest combination therapy, they’re more effective but come in with their own toxicity. The idea was to try [to] identify a group that might be definitely benefiting from this a lot more than the other group, or a group that may not be benefiting. Well, what we saw [was] that regardless of sensitivity to prior endocrine therapy, [a] disease-free interval from their prior treatment, choice of hormonal therapy, premenopausal status, [the] presence of visceral disease or bone-only disease, there was certainly a benefit across all patient characteristics and all subgroups to justify the use of a CDK4/6 inhibitor with endocrine therapy. So I have definitely been using this combination therapy in the first-line and second-line setting for my patients.

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