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SABCS 2022 | Hot topics in breast cancer in 2023 – what is coming next?

Hope Rugo, MD, Helen Diller Family Comprehensive Cancer Center, talks on hot topics in breast cancer. In triple-negative breast cancer (TNBC), research is focusing on improving outcome in both metastatic and early stage setting. Several trials are being designed using antibody-drug conjugates (ADCs) in patients who don’t have a pathologic complete response (pCR) to neoadjuvant therapy, as well as individualizing and optimizing therapy based on patients tumor response, both by investigating shorter and less intensive regimens in the neoadjuvant setting and avoiding treatment in the post-neoadjuvant setting for patients who achieve pCR. Increasing data is uncovering which patients with HR-positive breast cancer benefit from immunotherapy and chemotherapy in the neoadjuvant setting. ADCs are being moved into the first-line setting, including trastuzumab deruxtecan which is also under investigation in the post-neoadjuvant and neoadjuvant setting. Additionally, focus on safety and patient-reported outcomes (PROs) is increasing. This interview took place at the San Antonio Breast Cancer Symposium (SABCS) 2022 in San Antonio, TX.

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Transcript (edited for clarity)

It’s such a big question to talk about what we’re excited about, and there are so many things to be excited about, I think, in each subgroup of breast cancer. We may not have all those results by 2023 though. So, I think, we’re looking for, first, in triple-negative breast cancer, trying to improve outcome both in the metastatic but also the early-stage setting. So, there are several trials being designed using antibody-drug conjugates in patients who don’t have a pathologic complete response to neoadjuvant therapy and most neoadjuvant therapy now includes pembrolizumab as part of our regimen...

It’s such a big question to talk about what we’re excited about, and there are so many things to be excited about, I think, in each subgroup of breast cancer. We may not have all those results by 2023 though. So, I think, we’re looking for, first, in triple-negative breast cancer, trying to improve outcome both in the metastatic but also the early-stage setting. So, there are several trials being designed using antibody-drug conjugates in patients who don’t have a pathologic complete response to neoadjuvant therapy and most neoadjuvant therapy now includes pembrolizumab as part of our regimen. So, that’s I think an incredibly important approach. And also trying to minimize the amount of treatment we give an individualized and optimized therapy for the patient’s own tumor response, both by testing shorter, less intensive regimens in the neoadjuvant setting, and also by maybe, stopping the treatment we give post-neoadjuvant setting, like not giving pembro to patients who have a pathologic complete response to try and reduce the immune toxicities and cost. So, that’s one exciting area.

In the metastatic setting, we’re looking at trying to give antibody-drug conjugates earlier with new partners. The concept of giving ADCs with these checkpoint inhibitors is really interesting and is being studied. There are new agents targeting different pathways. We’re trying to understand the benefit for in triple-negative breast cancer and all of that I think, is really critical because this is still such a big unmet need. In hormone receptor-positive disease, obviously, we’re looking for additional data even to support the use of CDK4/6 inhbitors. The NATALEE trial looked at ribociclib for three years, we’re thinking we might see the first data next year in, again, high-risk patient population, although, defined differently than monarchE. So, that’ll be very interesting. There’s increasing data that’s helping us to understand which patients with hormone receptor-positive disease can benefit from immunotherapy and chemotherapy in the neoadjuvant setting.

And I hope that we’re able to apply that data more broadly to clinical trials to try and understand who is going to benefit from this more intensive approach. And maybe, we could substitute the chemotherapy we’re giving now with antibody-drug conjugates in that subset of patients who already benefit from chemo and spare them the intensity of treatment. So, that’s actually a really exciting area too. And we can give these ADCs with checkpoint inhibitors, so that’s great.

So, that’s another really exciting area. We’re moving the antibody-drug conjugates earlier in the lines of metastatic treatment and trying to understand HER2-low and how low you can go is a huge area, discussed a lot at San Antonio, and I think, in another year, we’ll have a lot more data on this as well. Although, we may not have the answers yet. All of the ADCs are moving into the first line setting, as I mentioned, also in the post-neoadjuvant setting in specific subgroups of patients, and I think that will be really interesting.

And then in HER2-positive disease T-DXd are amazing antibody-drug conjugate, with amazing results here at San Antonio, 2022, is being moved in the first-line setting and is being studied as post-neoadjuvant and neoadjuvant therapy in HER2-positive disease. We’re looking at different combinations to try and prevent the development of brain metastases and treat them earlier and better so that we can help patients live longer in that setting, but also not have these unexpected brain metastases.

And then, I think, the other thing that’s really important is that there’s been an increasing focus on safety and patient reported outcomes, and that’s really great because we’re taking some of these new agents and being able to understand the safety and how to manage the safety of the drugs earlier. That’s, to me, very exciting too, that we’re really trying to incorporate patient reported outcomes and safety and meld them together to try and understand who’s at risk and to try and manage these toxicities earlier to improve the quality of life of our patients.

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