HR+ Breast Cancer: Factors in Selecting First-Line Therapy for Metastatic Disease


Highlights from key clinical data informing the selection of targeted therapy in particular subsets of patients with HR+ breast cancer.

Jules Cohen, MD:
Dr Slamon, perhaps you can speak to some of the abstracts that were presented at the San Antonio Breast Cancer Symposium. How do the following factors impact your treatment choices: the menopausal status of the patient and the presence and absence of visceral disease?

Dennis J. Slamon, MD, PhD: Let’s start with the latter 1 and work our way back. This question of visceral disease and the knee-jerk response that indicates you have to default to chemotherapy probably needs to go away. It’s something that has been overplayed and overused. There are data to support that this doesn’t make a difference. In particular, if you look at combined data from a number of studies looking at modern chemotherapy regimens¾either monotherapy drugs or taxane-containing combinations¾the outcome with hormonal blockade and a CDK4/6 inhibitor is superior both in terms of response rate and progression-free survival. The idea that you can’t use this, and that you have to intercede immediately because it’s a real problem, is incorrect.

In addition, when you look at time to response with CDK4/6 inhibitors, it’s not long. If you’re going to get a patient response, after the first month or 2, if you’re following something that’s palpable clinically or you have imaging data. For all those reasons, it seems unlikely that you’ll need to default to chemotherapy unless there’s something called visceral crisis. Even then, I’d think hard about not first going to a CDK4/6 inhibitor.

In terms of premenopausal disease, the MONALEESA suite of studies included a premenopausal study that clearly indicated that hormonal blockade plus a CDK4/6 inhibitor had a very similar benefit in that population. Menopausal status wouldn’t affect my decision to engage with a CDK4/6 inhibitor.

Jules Cohen, MD: Perfect. We saw very impressive results with the RIGHT Choice trial presented at San Antonio, right?

Joanne Mortimer, MD, FACP, FASCO: Yeah. It’s fascinating that they were able to do this study because this was first-line therapy in patients who had, as some people might define it, a visceral crisis disease because they could have had abdominal pain, significant liver disease, or other parenchymal disease with symptoms related to it. In the past, a lot of people would have gone right to chemotherapy. This was a trial that randomized patients to ribociclib [Kisqali] plus an AI [aromatase inhibitor] or tamoxifen [Nolvadex] and compared it with physician’s choice of chemotherapy. They were weird choices of chemotherapy. All of them were doublets of chemotherapy, but the bottom line was that the progression-free survival was double for ribociclib with endocrine therapy compared with chemotherapy. To reiterate what Dennis said, these are important data because it’s not only less toxic, but it’s better. Going right to chemotherapy isn’t the answer in these patients.

Jules Cohen, MD: Do you think that’s a US thing or a community practice thing? Are people still using a lot of chemotherapy in the first line for ER [estrogen receptor]–positive cancer to your knowledge?

Neil M. Iyengar, MD: There was this notion that chemotherapy acts quickly and should be used for high-burden metastatic disease, particularly visceral disease. The recent data, particularly with CDK4/6 inhibition, tells us that that notion isn’t correct. I’ve been struck by the objective response rates to CDK4/6 inhibition plus endocrine therapy, which are better than chemotherapy. From that standpoint, that would argue for using that combination, which is better at controlling disease. This is particularly substantial when disease control is important, like high-burden and visceral crisis disease. That’s going away. Parts of the world still default to chemotherapy in the setting of visceral disease. With all these data coming out, particularly the RIGHT Choice trial and the abemaciclib trial, the notion that we need to reach for chemotherapy will hopefully go away. We can now spare individuals from chemotherapy.

Jules Cohen, MD: What’s your prescription for this patient? What should she get? She was on anastrozole [Arimidex] for 2½ years and then relapsed in the liver.

Neil M. Iyengar, MD: This is a patient I’d consider using fulvestrant for, particularly given her relapse on an AI. I’d also consider clinical trial availability, particularly ongoing trials combining oral SERDs [selective estrogen receptor degraders] with CDK4/6 inhibition. In terms of standard of care, this is a patient I’d offer fulvestrant plus ribociclib.

Jules Cohen, MD: But if she had completed her anastrozole for 5 or 10 years—whatever was decided on—you might offer her another treatment. Let’s say she was 2 years off medication and then relapsed. In that case, you’d probably use a different aromatase inhibitor.

Neil M. Iyengar, MD: With a 2-year disease-free interval, I’d be comfortable using an AI plus CDK4/6 inhibition.

Transcript edited for clarity.

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