Recurrent HR+ Breast Cancer - Episode 2
Joyce O’Shaughnessy, MD:This patient has now presented with some mildly symptomatic liver metastasis. She’s got some fatigue and some intermittent nausea. The CT scan shows relatively smaller-volume liver metastasis, and it’s likely that her liver function is still good to just mildly abnormal.
In older years we would have considered chemotherapy for this patient. But now we have very good evidence that CDK4/6 inhibitors work as quickly as chemotherapy with much less toxicitybut most important, the CDK4/6 inhibitors, the duration of response in the median progression-free survival, are far superior to chemotherapy. In fact, we are seeing a sea change away from chemotherapy in the first-line metastatic setting to CDK4/6 inhibitors, with the exception being someone who is in absolutely frank visceral crisis, in which case we would still utilize combination chemotherapy for that patient. Otherwise, we really should be looking at a CDK4/6 inhibitor with endocrine therapy for virtually everybody with first-line metastatic breast cancer.
There are 3 CDK4/6 inhibitors, all of which have been evaluated extensively in first-line and second-line metastatic breast cancer in combination with an aromatase inhibitor, first line, or with fulvestrant second line. This patient’s disease has recurred on an aromatase inhibitor. So certainly we would be looking for fulvestrant with a CDK4/6 inhibitor. All 3 of the CKD4/6 inhibitorspalbociclib, ribociclib, and abemaciclib—have been studied extensively with fulvestrant in patients whose breast cancer has recurred on an aromatase inhibitor or within a year of finishing their adjuvant aromatase inhibitor therapy, or whose disease has recurred on adjuvant aromatase inhibitor therapy. So certainly I’d be comfortable with any of the CDK4/6 inhibitors. The data all look excellent, with all 3 of them yielding very similar reductions in the risk of progression from their breast cancer.
We recently received important data at the American Society of Clinical Oncology [ASCO] 2018 Annual Meeting on the MONALESSA-3 clinical trial. There were 2 groups of patients who were all postmenopausal women, and they had either progression of their disease or recurrence of their disease on an aromatase inhibitor. They received fulvestrant with or without ribociclib, or they were first-line metastatic and had no prior endocrine therapy for metastatic disease and were beyond 1 year following completion of their adjuvant endocrine therapy.
A more naive or sensitive population received an endocrine therapy and fulvestrant with or without ribociclib. That was kind of a unique population because all the other CDK4/6 inhibitor trials in the first-line setting utilize an aromatase inhibitor with or without a CDK4/6 inhibitor. Here are our first data in MONALESSA-3 with fulvestrant in the first line with ribociclib. Not surprisingly, the ribociclib very substantially improved progression-free survival, both in the first-line setting and in the second-line setting, putting all the data together in the overall treated population. The median progression-free survival went from about 12.8 months or so up to a little bit more than 20 monthsa large improvement in the median . These are very, very good data, which show the safety and efficacy of the ribociclib with the fulvestrant. This will be an excellent choice for this patient. The other 2 CDK4/6 inhibitors would also be excellent because they all look very similar with regard to their efficacy with fulvestrant.
We have had excellent data with the CDK4/6 inhibitors in general with fulvestrant. All 3 of the CDK4/6 inhibitors have very similar safety and efficacy data with fulvestrant in patients whose breast cancer has progressed under the aromatase inhibitor. What’s interesting and unique about the MONALESSA-3 study is it gave us unique data for first-line fulvestrant in combination with ribociclib; it looked quite excellent.
The other studies that have looked at fulvestrant in combination with a CDK4/6 inhibitor are PALOMA 3 with palbociclib, and the MONARCH 2 with abemaciclib. Just like the MONALESSA-3 in your aromatase inhibitor pretreated population, the addition of the CDK4/6 inhibitor to fulvestrant, regardless of the CDK4/6 inhibitor, really looked excellent. We’re seeing unanimity of the effectiveness across the board with the CDK4/6 inhibitors.
Transcript edited for clarity.
A 58-Year-Old Woman With Recurrent HR+ Breast Cancer