A Case of Estrogen-Driven Metastatic Breast Cancer - Episode 6

Evolving Treatment Options in ER+ Metastatic Breast Cancer

Komal Jhaveri, MD, FACP:If our patient is asymptomatic, which she was, and had only the de nova metastatic disease to the bone that we talked about, without having significant pain, you might recall that we detected her [suspected] bone lesions with that biopsy just because we did a CT scan and a staging workup. The patient did not present with those symptoms. So I think my therapy would still remain the same with a CDK4/6 inhibitor with endocrine therapy for this woman.

That actually brings us to a very common question that we want answered in clinic when we’re seeing a patient with first line, for first-line recommendations of treatment for metastatic disease. When we really think that the patient is in visceral crisis, when we talk about the patient as being symptomatic, are we talking about a mild cough? Are we talking about some shortness of breath? Or are we talking about a woman who [is] significantly short of breath, has significant difficulty with [coughing], we’re seeing that her vital signs are being compromised. She’s having difficulty breathing or maintaining the saturations at room temperature, and we’re thinking about perhaps giving them chemotherapy, thinking that maybe chemotherapy might have a faster impact.

But short of that, if a patient does not advance with visceral crisis, meaning with a significant disease burden or a lot of symptoms or a lack of modalities that go along with the symptoms, I think it’s very, very appropriate to treat this woman with a combination [of] a CDK4/6 inhibitor with endocrine therapy.

We treated this woman with fulvestrant with ribociclib in the first-line setting. So if this woman were to progress, at that point I think it would be very appropriate should she not have any significant disease burden with a lot of visceral crises to continue to treat her with endocrine therapy. And you could use and justify the combination of eczema stain with everolimus or tamoxifen with everolimus, based on the results from the BOLERO-2 or the TAMRAD trials, and treat her in the second-line setting with that combination. In fact, when you look at the [National Comprehensive Cancer Network] guidelines, they suggest that a woman with [estrogen receptor] (ER)-positive metastatic disease can be treated with up to 3 lines of endocrine therapy before you have to resort to chemotherapy. Certainly, if there was an appropriate clinical trial option available for her, I would gladly be enrolling her in that clinical trial and reserving exemestane and everolimus or tamoxifen and everolimus in the third-line setting before I had to [resort] to chemotherapy.

We have come a really long way. So we used to treat our postmenopausal women only with aromatase inhibitors. And now we have data for CDK4/6 inhibitors with aromatase inhibitors based on the randomized phase III trials that all unanimously have shown an unprecedented benefit in progression-free survival for these women.

We also now have a glimpse of activity and justification that we can use in clinic to utilize fulvestrant with CDK4/6 inhibitor based on the MONALEESA-3 trial, and fulvestrant alone based on the FALCON trial.

There is an important study, I think, which is actually evaluating head-to-head fulvestrant plus a CDK4/6 inhibitor, in this case palbociclib, with aromatase inhibitors and palbociclib..

We do have an important trial that we’re awaiting the results from, which is comparing fulvestrant with a CDK4/6 inhibitor. In this case, palbociclib, compared [with] aromatase inhibitors with palbociclib, based on the PARSIFAL study, and hopefully that will also shed light into whether there is a very appropriate and the best endocrine therapy partner that we should certainly be thinking about in the first-line setting. But until then, I think we definitely have a lot of data to justify CDK4/6 for our patients in the first-line setting, specifically with aromatase inhibitors and now also with fulvestrant.

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