Additional Advances in Triple-Negative Breast Cancer Research and Clinical Trials With Sara M. Tolaney, MD, MPH

Last year, Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, served as co-chair of i3 Health’s webinar and online activity, Pathology and Oncology Expert Perspectives in the Management of Triple-Negative Breast Cancer (TNBC). With numerous advances in TNBC research occurring since then, Dr. Tolaney sat down with Oncology Data Advisor to share additional updates from clinical trials and a preview into the future of treatment with emerging therapies for TNBC. 

This interview is also available as a podcast. Click here to listen!

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, I am joined by Dr. Sara Tolaney, who served as co-chair last year of i3 Health’s triple-negative breast cancer webinar. Dr. Tolaney is now sitting down with us again to share additional updates in TNBC research that have occurred since this webinar was recorded last July. Dr. Tolaney, great to have you on again today.

Sara M. Tolaney, MD, MPH: Thank you so much for having me. My name is Sara Tolaney. I’m a Breast Medical Oncologist at Dana-Farber Cancer Institute and Chief of our Breast Program here. My interests stem around drug development. I’m really interested in trying to move more effective therapies forward for treating our breast cancer patients, but also trying to balance that with mitigating toxicities to try to make sure we give the right amount of treatment to the right patient.

Oncology Data Advisor: Awesome. Since this webinar was recorded last July, have there been any new advances in TNBC treatment and management that have occurred?

Dr. Tolaney: Over time, there’ve been several advances for treatment of metastatic triple-negative breast cancer. Originally, we only had chemotherapy for triple-negative disease, then along came immunotherapy, which has had benefit for the subgroup of patients that have programmed death-ligand 1 (PD-L1)–positive tumors. We also have had introduction of poly-ADP ribose polymerase (PARP) inhibitors for patients that have germline BRCA mutations.

More recently, we’ve seen introduction of antibody-drug conjugates (ADCs) such as sacituzumab govitecan and also trastuzumab deruxtecan (T-DXd), which is specifically for the subset of triple-negative breast cancer patients who are human epidermal growth factor receptor 2 (HER2)–low. I do think these more recent advances with antibody-drug conjugates have been really exciting for our patients.

Oncology Data Advisor: That’s really exciting. Are there any ongoing trials or research that you’re looking forward to seeing results of in the near future?

Dr. Tolaney: We’re really excited about some of the trials that are trying to move antibody-drug conjugates earlier. For example, there are trials that are combining antibody-drug conjugates with immunotherapy in the first-line setting. The ASCENT-04 trial, for example, is combining sacituzumab with pembrolizumab in the first-line, triple-negative, PD-L1-positive setting. The TROPION-Breast05 trial, likewise, is combining datopotamab deruxtecan with durvalumab in that upfront setting. Then there are also trials looking at either sacituzumab govitecan in ASCENT-03 or datopotamab deruxtecan (data-DXd) in TROPION-Breast02 in the first-line triple-negative setting.

To me, those are really important studies because they will help us understand if antibody-drug conjugates can be used upfront and could allow us to have another ADC for triple-negative disease, which would be dato-DXd and other TROP2-directed ADCs.

Oncology Data Advisor: Absolutely. Are you currently involved in any TNBC research that you’d like to highlight?

Dr. Tolaney: I think there’s a lot of interesting questions in triple-negative disease. One question that our group has had a lot of interest in trying to understand is, can you give antibody-drug conjugates sequentially? And how do they actually work, one after another? We have availability of both sacituzumab govitecan and T-DXd right now, and we think soon we may also have datopotamab deruxtecan. The question will be, how do you actually use these, and are there some patients who can benefit from sequential therapy?

Along with one of my colleagues, Ana Garrido-Castro, we’re running a trial called TRADE-DXd, which is looking at sequential use of T-DXd and dato-DXd, giving one before the other or switching them around and seeing what order works best and how the second ADC performs after the first. Importantly, the study will collect biospecimens because that will really help us understand if there are resistance mechanisms that are arising to a particular ADC that make us understand that another ADC won’t work, or are there other factors that help us understand why an ADC may work particularly well in a certain patient? I think we have a lot to learn here, so hopefully these types of studies will get us some-

Oncology Data Advisor: With all these ongoing directions, what are you most looking forward to seeing in the treatment and management of TNBC within the next few years?

Dr. Tolaney: My hope is that we’re going to get to a point where we are able to deliver more personalized therapy. I think, unfortunately, triple-negative disease has been coined with this term, which is defined by what it isn’t. It does not have estrogen receptor (ER)/progesterone receptor (PR) and HER2 expression, but clearly it does have other protein expression. We know, for example, it has TROP2, and some have HER2. Some may have homologous recombination deficiency. Some may harbor germline BRCA mutation or germline PALB2.

I think we need to get to a point where we can understand what drug a patient needs based on the biology of their tumor at that point in time. Clearly, it also evolves as patients get therapy, and we need to be able to figure out what treatment makes sense for them based on biomarkers, not just based on what the standard first-line treatment is. We need to know for that individual patient. My hope is that over the next several years, we’ll be able to get there.

Oncology Data Advisor: Awesome. My last question for you is, do you have any words or messages for clinicians who are treating TNBC, whether regarding treatment or toxicity management?

Dr. Tolaney: I think for right now, the critical pieces of information to make sure we have about a patient who’s starting therapy for metastatic triple-negative disease is to really make sure that we’ve checked for things like PD-L1, that we know if they have a germline genetic mutation like BRCA or PALB2, that we’ve done next-generation sequencing—to know, for example, if the tumor could have a high tumor mutation burden or be microsatellite instability (MSI)–high—and then we’ve also looked to see if the tumor could be HER2-low. Having all those pieces of information at least allows us to understand what therapies make sense. I think it is critical to make sure that we’re obtaining. Sometimes there’s so much going on with the patients that we don’t always remember to check all of those things, but it’s really critical so that we can make sure we get the right treatment for that patient.

Oncology Data Advisor: Great, thanks so much for sharing all of this today. For everybody listening, I will encourage everyone to visit to view Dr. Tolaney and Dr. Ira Bleiweiss’s full CME/NCPD activity and claim credit. Thank you so much, Dr. Tolaney, for sharing all these updates today.

Dr. Tolaney: Thank you so much.

About Dr. Tolaney

Sara M. Tolaney, MD, MPH, is Chief of the Division of Breast Oncology and Associate Director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute. She is also an Associate Professor of Medicine at Harvard Medical School. Dr. Tolaney’s research focuses on the development of novel therapeutic strategies for breast cancer, including de-escalation of therapies for patients with low-risk HER2-positive disease, and she has been instrumental in the development of CDK4/6 inhibitors and immunotherapies for breast cancer. 

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor.

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