Medical Oncology Research at the Miami Breast Cancer Conference
The recent Miami Breast Cancer Conference was a combined virtual and on-site meeting, providing an opportunity for breast cancer specialists from all disciplines to learn about emerging therapeutic strategies to be translated into clinical practice.
In this exclusive MedPage today video, conference co-chair Debu Tripathy, MDfrom the University of Texas MD Anderson Cancer Center in Houstondetails the medical oncology research presented at the conference.
Here is a transcript of his remarks:
Hello, my name is Debu Tripathy. I am a professor and chair of the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center. And I’m pleased to update you on some of the findings and some of the discussions that we had at the Miami Breast Cancer Conference. And I’m going to focus on those that involve the field of medical oncology, especially new therapeutics, and that’s best covered by discussing the different subtypes of breast cancer.
So let’s start with hormone receptor positive breast cancer. And we explained how, at the early stage, we now have growing evidence that ovarian suppression is important for premenopausal patients with hormone receptor positive and HER2 negative breast cancer. Updates from the TEXT and SOFT trials now show a 3-5% reduction in disease-free distant recurrence, especially in high-risk patients.
There are still questions about how to optimally suppress ovarian function. Whether depo-gonadotropin analogues can be used or not. We just don’t know those answers right now. The recommendation is to use the monthly medications that have been shown to be effective in this situation and to ensure that high-risk patients – those with a positive node or those in need of chemotherapy – are treated.
In the advanced setting, there has been a lot of movement, especially with the development of selective estrogen receptor negative regulators. And it’s a very interesting story because with estrogen suppressing therapies, especially with aromatase inhibitors, we see the evolution or development of estrogen receptor mutations.
the CSR1 The gene that codes for the estrogen receptor may be mutated in up to 30-40% of patients who have progressed after treatment with an aromatase inhibitor. Selective estrogen receptor downregulators should theoretically be able to downregulate even the mutant form of the estrogen receptor, which signals autonomously even in the absence of estrogen.
And in fact, the first of these randomized trials was presented at [the San Antonio Breast Cancer Symposium] and reviewed at the Miami Breast Cancer Conference. And it is with the drug elacestrant, which is one of the selective negative regulators of estrogen receptors [SERDs]. It is taken orally and has been compared with fulvestrant in patients who have already received one or two endocrine treatments. And that showed a big step up from fulvestrant and is currently being reviewed by the FDA, and that could become a new standard.
I think we still have a lot to learn about these SERDs. There are many that are currently in randomized clinical trials, but the more relevant question will be how they combine with the biological therapies that we use as first line, with CDK [cyclin-dependent kinase) inhibitors or with everolimus, or in the case of PIK3CA mutations in combinations with alpelisib. So those kinds of trials are pending.
Let’s now move to HER2-positive breast cancer, where again there has been rapid evolution and changes, with trastuzumab deruxtecan now moving to the preferred agent in second-line therapy on the basis of the DESTINY B03 study, which showed a clear superiority of trastuzumab deruxtecan over T-DM1. So that’s really going to shift how we treat patients.
We discussed some of the newer antibody drug conjugates that are coming on the horizon — trastuzumab duocarmazine, which in the TULIP randomized trial showed a superiority over chemotherapy of physician’s choice. And there are going to be other antibody drug conjugates that are going to be tested.
And then the breaking news that just came out from DESTINY BREAST04, which is looking at HER2 low-expressing cases. And again showed that in comparison to chemotherapy of physician’s choice that trastuzumab deruxtecan was superior. So this is brand new data that is now being evaluated by the FDA.
And then in the area of triple-negative breast cancers, there’s also been a lot of movement there, with sacituzumab govitecan recently being approved and now moving into second-line, maybe third-line, therapy. But there are trials now examining this drug in even earlier stages, and there’s other antibody drug conjugates targeting triple negative, such as Dato-DXd, and we’re looking forward to seeing more data. So far, just the phase I triple-negative subset has been reported, that is showing activity.
In the area of immunotherapy we actually had a very lively debate about the use of immunotherapy, and I will focus on the KEYNOTE-522 study, which is really the most recent development in that area, showing a clear advantage of adding pembrolizumab to a standard backbone that actually includes carboplatin.
So carboplatin and [paclitaxel] followed by doxorubicin and cyclophosphamide with or without pembrolizumab was the study design. And then patients were also randomized after surgery to receive either nine more pembrolizumab treatments or a placebo. And this study showed a clear benefit, not only in pathological complete response, but especially in event-free survival, which led to its endorsement in this setting. And now the follow-up data from this study shows what an early survival advantage is, although it doesn’t quite meet the threshold because the data is still immature.
One of the things we’ve discussed is whether or not patients who get a pathological complete response [pCR] need to go for more pembrolizumab adjuvant or not because the results are really great in this group. They are more than 90% in patients who obtain a pCR with only a 2% difference, which is really not very different.
Sure, the study was empowered to look at this group, but with a good result, should further therapy be given? And the debate went back and forth; obviously the trial was designed that way. We therefore generally recommend monitoring the use of pembrolizumab even with a pathological complete response.
But the public after the debate ended may not have actually always felt – you know, there are additional toxicities that patients get during the maintenance phase. And there will actually be a trial looking at a randomization of whether or not to receive the adjuvant part of checkpoint inhibitor therapy after pCR.
So there are many other questions that need to be answered about whether we are able to defuse the appropriate patients. And you’re going to see more trials in this space.
And then in the field of immunotherapy in general, there are many new drugs that can potentiate the action of checkpoint inhibitors, in particular those that deal with innate immunity that are going to appear. And we will talk about it in future meetings.
So it’s a whirlwind tour of the medical oncology aspects of what was presented at the Miami Breast Cancer Conference.