番茄社区

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 translate into clinical practice.

In this exclusive 番茄社区 video, conference co-chair , of the University of Texas MD Anderson Cancer Center in Houston, details the medical oncology research presented at the conference.

Following is a transcript of his remarks:

Hello, my name is Debu Tripathy. I'm a professor and chairman of the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center. And it's my pleasure 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 medical oncology area, particularly new therapeutics, and it's easier to cover it discussing the different subtypes of breast cancer.

So let's start with hormone receptor positive breast cancer. And we spoke about how in the early-stage setting, that we now have growing evidence that ovarian suppression is important for premenopausal patients with hormone receptor positive and HER2-negative breast cancers. Updates from the TEXT and SOFT trials are now showing anywhere from a 3 to 5% reduction in distant disease-free recurrence, especially in the higher-risk patients.

There's still some questions as to how to optimally suppress ovarian function. Whether depo-gonadotropin analogues can be used or not. We simply don't know those answers right now. The recommendation is for using the monthly drugs that have been shown to be effective in this situation, and to ensure that higher-risk patients -- those that are node positive or those that needed chemotherapy -- are treated.

In the advanced setting, there has been a lot of movement in particular with the development of selective estrogen receptor downregulators. And this is a very interesting story because with estrogen-suppressing therapy, particularly with aromatase inhibitors, we are seeing the evolution or the development of estrogen receptor mutations.

The ESR1 gene that encodes for the estrogen receptor can be mutated in up to 30-40% of patients that have progressed after aromatase inhibitor therapy. Selective estrogen receptor downregulators theoretically should 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 those randomized trials was presented at [the San Antonio Breast Cancer Symposium] and reviewed at the Miami Breast Cancer Conference. And this is with the drug elacestrant, which is one of the selective estrogen receptor downregulators [SERDs]. It's given orally, and was compared to fulvestrant in patients who had had one or two prior endocrine therapies. And that showed a clear advance over fulvestrant and is now under review by the FDA, and that may become a new standard.

I think there's much more we need to learn about these SERDs. There are many of them that are now in randomized clinical trials, but the more relevant question is going to be how they pair up with biological therapies that we're using in the first-line setting, 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 design of the study. And then patients were also randomized following surgery to either receive nine more treatments of pembrolizumab or placebo. And that study showed a clear advantage, not only in complete pathologic response, but more importantly event-free survival, which led to its approval in that setting. And now follow-up data from that study is showing what is an early survival advantage, although not quite meeting the threshold as the data are still immature.

One of the things we discussed is whether or not patients who achieve a pathologic complete response [pCR] need to go on to get further adjuvant pembrolizumab or not, because the outcomes are really excellent in that group. They are over 90% in patients that achieve a pCR with only a 2% difference, which really is not very different.

Certainly the study was empowered to look at that group, but with a good outcome, does there need to be additional therapy given? And the debate went back and forth; obviously the trial was designed that way. So we would generally recommend that we do follow the use of pembrolizumab even with a complete pathologic response.

But the audience after the end of the debate actually felt maybe not always -- you know there are some added toxicities that patients get during the maintenance phase. And there is actually going to be a trial that does look at a randomization to receive or not the adjuvant portion of a checkpoint inhibitor therapy after a pCR.

So there are many other questions that need to be answered in terms of whether we're able to deescalate the appropriate patients. And you are 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, particularly those that deal with innate immunity that are going to be coming onto the scene. And we will cover those in future meetings.

So that's a whirlwind tour of the medical oncologic aspects of what was presented at the Miami Breast Cancer Conference.

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