Dr Gatti-Mays Speaks on Advances in Triple Negative Breast Cancer

Dr Gatti-Mays Speaks on Advances in Triple Negative Breast Cancer

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In this video, Dr Gatti-Mays speaks on the exciting advancements in triple-negative breast cancer.

 

Transcript: 

Good afternoon, my name is Dr Margaret Gatti‑Mays. I'm a medical oncologist and assistant professor at The Ohio State University in Columbus, Ohio. My preferred pronouns are she/her. My focus in clinical and research is breast immunotherapy, so today I'm going to talk about some of the advances in triple‑negative breast cancer, and specifically focus on metastatic triple‑negative breast cancer.

The current standard of care in terms of systemic therapy for triple‑negative breast cancer is chemotherapy plus or minus immunotherapy. Now this is both in the neoadjuvant or early setting, as well as in the metastatic or advanced setting. Currently, though, there's a limited role for immunotherapy in the adjuvant setting, meaning after surgery. In patients who have received neoadjuvant chemotherapy and immunotherapy, these patients can continue pembrolizumab, but there's very limited role for starting pembrolizumab in the adjuvant therapy. All of these indications for the use of immunotherapy in triple‑negative breast cancer have been relatively recent approvals and recent changes in standard of care. It's been a very exciting time to be in breast cancer but specifically, in breast cancer and immunotherapy.

Within the last few years, we've been able to show that the addition of immunotherapy to chemotherapy in breast cancer significantly improves outcomes. We first saw this with the approval of atezolizumab and nab‑paclitaxel back in 2019 for use in first‑line metastatic triple‑negative breast cancer. The IMpassion130 trial showed that there was a clinically significant improvement in progression‑free survival, as well as overall survival in those patients that were PDL1‑positive, which was graded according to the SP142 assay for PDL1. Unfortunately, this approval for atezolizumab in the first‑line setting was recently withdrawn by the pharmaceutical company due to the confirmation trial, which was IMpassion131, failing to meet its survival outcome. However, despite this, the atezolizumab was the groundbreaker in using immunotherapy successfully in triple‑negative breast cancer. After this trial, we started to have an array of keynote trials that were specifically in breast cancer that showed promise for using immunotherapy in these hard‑to‑treat triple‑negative breast cancers.

First, we saw the approval of pembrolizumab with chemotherapy in the first‑line metastatic setting for triple‑negative breast cancer and that was based on the KEYNOTE‑355 clinical trial, which again, showed an improvement in progression‑free survival as well as overall survival. In the first‑line metastatic setting, we can use pembrolizumab plus or minus a chemotherapy that either is nab‑paclitaxel, paclitaxel, or gemcitabine. Generally, they're all with pembrolizumab in the first‑line setting and it's very much up to the treating oncologist to decide the appropriate chemotherapy companion for their specific patient.

In terms of my preference for looking at those and choosing one of those agents, I generally do try to prioritize ataxin plus pembrolizumab, except in those patients who had rapidly recurred after treatment with neoadjuvant chemotherapy which included ataxin, or in those patients that had debilitating neuropathy from their prior chemotherapy regimens. In addition, gemcitabine and carboplatin may be preferred in patients with higher volume or more aggressive disease but, obviously in a disease like a triple‑negative breast cancer, this approval of pembrolizumab and the significant clinical gains were extremely exciting.

Following this approval in the advanced setting, there was also the approval of using pembrolizumab plus chemotherapy in the neoadjuvant or early setting in patients with high-risk triple‑negative breast cancer. This was recently approved this past summer in 2021 based upon the KEYNOTE‑522 clinical trial, which showed not only an improvement in pathologic complete response in patients who received pembrolizumab plus neoadjuvant chemotherapy, but we also saw an improvement in invasive disease‑free survival at three years and this was really exciting data because the other part that was exciting about this approval for pembrolizumab in the neoadjuvant setting was that the benefit of pembrolizumab extended to not only patients whose tumors were PDL1 positive, but to those patients that were PDL1 negative as well.

In the neoadjuvant setting, irrespective of PDL1 status, in these high‑risk triple‑negative breast cancer patients, with tumors that are generally greater than two centimeters, or in those patients that have lymph node positive, the addition of pembrolizumab to chemotherapy significantly improved outcomes both in the short‑term, with improvement in pathologic complete response, as well as in the long‑term, with improvement in three‑year invasive disease‑free survival. All of this, obviously, has been very exciting in the triple‑negative realm and I think when we look back over the last 10 years, we've seen what an incredible impact research can have in terms of directing standard of care therapies and improving outcomes for patients with standardly difficult‑to‑treat cancers.

In terms of where the field of immunotherapy and breast cancer is going, that's specifically one of my interests in clinical research. My focus is primarily on translational, so bringing some of the early clinical or early preclinical data from the lab into the clinical setting and I think as we've seen with these approvals, that while single‑agent immunotherapy did not have significant impacts in our breast cancer patients, that the combination of chemotherapy with immunotherapy or the combination of other agents with chemotherapy are much more promising for our patients.

In terms of some of the exciting data that's coming out, definitely looking at novel combinations of using immunotherapy, and whether that be immune checkpoint inhibitors, therapeutic cancer vaccines, or cellular therapies, like CAR-T cells or NK cell‑based therapies, these immunotherapies combined with standard therapies hold a lot of promise.

In addition, another area in triple‑negative breast cancer that's extremely exciting are antibody drug conjugates. The recently discussed datopotamab deruxtican, which is a similar antibody drug conjugate to trastuzumab deruxtican, which is used in the HER2 setting. With datopotamab deruxtican, we saw very nice improvement in terms of responses. We also saw very good disease control in patients with pre‑treated triple‑negative breast cancer, so we currently have already one approved antibody drug conjugate with this sacituzumab govitecan, and this datopotamab deruxtican is another promising antibody drug conjugate.

In summarizing those agents that I've just spoken about and in terms of the recent approval of immunotherapy agents with chemotherapy, and again, that was atezolizumab and pembrolizumab, in addition to chemotherapy, both in the early as well as metastatic settings. The approval of sacituzumab govitecan, which also was recent, and also, has made a significant impact in some of these patients with triple‑negative breast cancers who have progressed now on several therapies. The future of triple‑negative breast cancer in immunotherapy is combinations, as well as some of these novel therapeutic agents.

In terms of what do I specifically find encouraging about these, is again, if we look back over the last 10 years, there's been a boom in agents in novel antibodies but also, significant clinical advances, in terms of our patients are doing better for longer, quality of life is relatively good on many of these treatments, and it's not to say that there aren't toxicities but, as we think in the metastatic setting for many of our patients, it really is a marathon. Being able to have multiple options that we can use sequentially is very exciting. Of course, at this point, we are unsure of the optimal sequence and that's obviously something that in the years to come, will hopefully be ironed out a little bit better. Again, when we look at these agents, the reason that there have been advances in a cancer like triple‑negative breast cancer is because of patients who were willing to participate in clinical trials.

As somebody who works in clinical trials, who runs clinical trials, I'm extremely grateful to our patients who decide to participate in clinical trials because in some instances, patients will directly benefit from clinical trials but, it’s a very selfless act, and one that as we can see based upon the advances in triple‑negative over the last decade, that this was all made possible by patients who were willing and able to participate in clinical trials.

In terms of some of the other immediate action items that we as oncologists need to address, when considering clinical trial eligibility, considering who enrolls on clinical trials, we as oncologists have to do a much better job of getting our patient populations in clinical trials to be more representative of the patients that we see in clinic. For example, we tend to see fewer patients of African American descent or Hispanic on clinical trials and this is important, because we do see some differences in the tumor types, we see some differences in terms of metabolism of drugs, and it's difficult sometimes to extrapolate the data we see in clinical trials to the patients that we see in our clinic. We as oncologists have to do better about making sure that our clinical trial enrollments are representative of the patients that we treat, and to add to that, the other part of clinical trial eligibility is ensuring that patients who are in much need of clinical treatments, like those patients with brain metastases or leptomeningeal disease, should be eligible for these clinical trials. Historically, patients with more advanced cancers, more difficult‑to‑treat brain metastases or leptomeningeal disease have been excluded from clinical trials but, again, these are the patients that need these options the most. In terms of action items, those are at the top of my list in terms of what we need to do to better serve our patients.

In summary, it's a really exciting time and a very hopeful time to be in breast cancer research and I think the future of immunotherapy in breast cancer is very bright and is very exciting.