Considerations for approaching the treatment of HR-positive metastatic breast cancer through insights on key prognostic factors.
Andrew D. Seidman, MD: Nick, we talk about hormone receptor–positive HER2-negative breast cancer almost as 1 big category of patients—in fact, it’s the largest piece of the breast cancer pie. But clearly there’s heterogeneity, not only as we’ve been talking about in terms of molecular features but also clinical features. How do you think about managing this population based on other features, endocrine resistance, and visceral involvement?
Nicholas McAndrew, MD, MSCE: Absolutely. It’s a really important question. First, I want to finish a further discussion about how to manage patients with an ESR1 mutation, especially given the fact that MONALEESA-3 has data in the first-line setting, in that the endocrine partner in that study was fulvestrant. It may not necessarily be actionable, but it would potentially push you to choose fulvestrant as an endocrine partner in the first-line setting with a CDK4/6 inhibitor as the partner. Especially given that a subset analysis of MONALEESA-3 that looked at patients with other activating mutations showed around 14% of patients had ESR1 mutations. Patients, regardless of any of these mutations that were found, showed benefit with the addition of ribociclib to fulvestrant. It’s important to get at baseline for a number of reasons.
In terms of other more clinically driven prognostic factors, menopausal status would certainly drive your choice of the endocrine therapy backbone. But it’s also important to consider whether the patient has de novo vs recurrent disease. What was their disease-free interval? In prior adjuvant therapy, did they progress on endocrine therapy, or did they have a long disease-free interval once they had completed adjuvant endocrine therapy? Or were they totally de novo from the get-go? I also think about the patient’s tumor burden and sites of disease. Finally, I strongly consider their performance status and ability to adhere to different types of therapies.
One of the most important questions that has driven the decision to choose either an endocrine-based therapy combined with molecular therapy vs chemotherapy has been the presence of visceral metastases and visceral crises. It’s recommended in patients with visceral crisis who are presenting with organ dysfunction as a result of their visceral metastases, but you can still consider chemotherapy. There are emerging data showing that the overall response rate is comparable, if not better, in patients receiving a combination of endocrine therapy and a CDK4/6 inhibitor. As noted by the Young-PEARL study, there was slightly better overall response rate in patients who had received the combination of ovarian suppression AI [aromatase inhibitor] plus a CDK inhibitor as compared with capecitabine. Even in patients who have visceral metastases who may not be in crisis, I would still consider using the combination regimen.
Andrew D. Seidman, MD: That’s a great observation. We’ve all been able to recalibrate our thinking about endocrine therapy vs chemotherapy in the context of visceral disease in the CDK4/6 inhibitor era.
Transcript Edited for Clarity