Closing out her discussion on the treatment and management of HR+/HER2- mBC, Hope Rugo, MD, FASCO, highlights unmet needs and future directions in the field.
Case: A 57-Year-Old Woman with HR+/HER2- Metastatic Breast Cancer
Presentation
Patient history
Physical exam, clinical workup, and imaging
Treatment/followup
Transcript:
Hope Rugo, MD, FASCO: Where do we go from here? We have our first oral SERD [selective estrogen receptor degrader], which is very exciting. It seems to have taken forever to get here. It’s great to have an oral SERD that’s approved and a specific patient population, with tumor mutations, that benefits from this. We also have some information about the criteria for patients who have more endocrine-sensitive diseases, using the surrogate marker of how long their disease was controlled on CDK4/6 inhibitors. This gives us an idea of which patients might benefit for a long time from elacestrant as a single agent. That’s a big step forward.
We already know about CDK4/6 inhibitors, but we need to understand if they work after progression. The postMONARCH trial, which is ongoing, will give us important data on that. We have a new targeted agent, the AKT inhibitor capivasertib. We’ll see ongoing data from that trial, waiting for survival data and events. It seems to be a drug that’s better tolerated than alpelisib, without as much hyperglycemia and with controllable rash and diarrhea. That will be a very important drug when it’s approved, we hope in 2023.
We have a whole host of oral SERDs and agents that work on the estrogen receptor. As I mentioned, ubiquitination with the PROTAC ARV-471. There are SERCAs—drugs that work by a different mechanism of ER [estrogen receptor] degradation—and oral SERDs. There are trials comparing single-agent oral SERDs to fulvestrant. Initial studies are looking at combinations, even triplets, with CDK4/6 inhibitors, and aromatase inhibitors in the early stage setting with some of our targeted agents. Someday they will also be combined with oral SERDs. Capivasertib will be combined with camizestrant, which is the same company as oral SERDs, and explored in combination with elacestrant once it’s approved. That’s important as well.
There are a lot of trial data that we’re going to see in the near future—maybe a 1-, 2-, 3-year time frame. We’re going to need to think about how we’re sequencing and using these agents. Of course, we have more targeted agents that are novel and more specific. PI3 kinase inhibitors cross the blood-brain barrier and work on a specific mutation, PIK3CA. There are oral SERDs that may work on specific ESR1 mutations or may work better on specific mutations vs others. We need to investigate that as we get more agents approved and have positive phase 3 data.
We’re still looking to see which patients with hormone receptor–positive disease benefit from immunotherapy. We’re trying to understand sequencing of antibody-drug conjugates and if using them earlier as first-line chemotherapy agents will be better. There are lots of studies going on, with lots of exciting data to look for in the future. We’re already making tremendous strides.
Transcript edited for clarity.
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September 25th 2020In season 1, episode 3 of Targeted Talks, the importance of precision medicine in breast cancer, and how that vitally differs in community oncology compared with academic settings, is the topic of discussion.
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