Duke Cancer Institute Faculty Describe Latest Efforts in Breast Cancer Research

In interviews during the 2019 OncLive^® State of the Science Summit™ on Breast Cancer, faculty from Duke Cancer Institute provided insight into the exciting breast cancer research being conducted at their institution.

Paul K. Marcom, MD

Paul K. Marcom, MD

Professor of Medicine, Duke Cancer Institute

“We have some very interesting work that’s going on with endocrine therapy resistance post-CDK4/6 inhibition. [We’re exploring] novel mechanisms [that will hopefully prompt] tumors to be more sensitive to novel therapies and be able to target things like apoptotic machinery in order to overcome that resistance.

I’m working with a colleague who has done some very elegant work in looking at disseminated tumor cells, how cells [spread] to the bone marrow space and hibernate, and the factors that control the entry and exit of those cells in ways that we’re hoping to target in a trial that we hope to be opening soon. I believe that speaks to the ability to target minimal residual disease and be able to finally find patients with high-risk disease, seemingly cured, but still are at high risk for recurrence, and understanding whether they have any disease burden or not and being able to target that with hopefully fairly nontoxic molecularly driven mechanisms.”

Carey K. Anders, MD

Carey K. Anders, MD

Medical Director, Brain and Spine Metastasis Center, Duke Cancer Institute

“We have an upcoming study called the ANGLeD study, which is a study of a compound called ANG1005, which is a novel taxane that is bound to angiopep. Angiopep binds to the LRP1 receptor on the blood-brain barrier, and it essentially shuttles the paclitaxel across the blood­-brain barrier and into the brain metastases themselves. In the early analysis of the ANG1005 compound, one patient population of great unmet medical need showed benefit, and that included patients with leptomeningeal carcinomatosis.

The ANGLeD study will be evaluating the ANG1005 compound compared with a physician’s choice list of therapies for patients with leptomeningeal disease. We’re very hopeful that this compound will prove fruitful for our patients because this can be a very challenging disease to treat, and predominantly, our therapies are intrathecal or delivered directly into the cerebrospinal fluid. Having an intravenous delivery method for an effective therapy would be fantastic for this patient population.”

Susan Faye Dent, MD

Susan Faye Dent, MD

Medical Oncologist, Duke Cancer Institute

“For me, my interest is in not just breast cancer, but in the cardio-oncology space. As such, UPBEAT, to me, is the first study I can think of where we’re actually looking at the adult population and long-term cardiovascular toxicity. There is a huge amount of data in the childhood cancer survivorship group.

Longitudinally, there has been a childhood cancer survivorship survey that has been carried out over decades, and from that data, [investigators have] been able to generate evidence-based guidelines on how to follow children as they reach adulthood. What we do know is that adults who have survived a childhood malignancy are at a significantly higher risk of cardiovascular disease at a much younger age. Although breast cancer is generally a disease [that presents] in postmenopausal women, we see women in their thirties and forties [diagnosed with it]. These women are potentially going to be living for several years.”

Jeremy Force, DO

Jeremy Force, DO

Medical Oncologist, Duke University

“I’d like to highlight the fact that we have [planned] studies [in which we will] utilize the oncolytic poliovirus to stimulate the local tumor immune microenvironment in combination with checkpoint blockade and/or with chemotherapy. We are in the process of getting those studies up and running and they will hopefully be [ready] in the near future. Similar to stimulating the immune system to be ready and then leverage that with immunotherapy such as checkpoint blockade is biologically rational, and we’re all very enthusiastic about the potential outcomes that this could have for our patients with triple-negative breast cancer.”

Gretchen G. Kimmick, MD, MS

Gretchen G. Kimmick, MD, MS

Professor of Medicine, Duke University Medical Center

“We have many clinical trials going on. There is some really exciting work being done with estrogen receptor (ER)—positive breast cancers that are looking specifically at inflammation. I have also been working with some of my colleagues to try to figure out how to improve adherence to endocrine therapy. We’re looking at symptom management and how to help patients better manage their symptoms so that they can stay on treatment longer. We had found that the risk of recurrence doesn’t matter as much to women [compared with] how much they’re dealing with day-to-day in terms of adverse events (AEs). We chose to focus on the AEs [in our work].

We’re also looking at diabetes and how to better help women manage their diabetes so that they can deal with their treatment with PI3K inhibitors. Diabetes increases the risk of breast cancer and breast cancer recurrence. As such, we’re focusing on how to help breast cancer survivors right now manage their diabetes in hopes of bringing that into an earlier setting. Perhaps if we managed diabetes more and have patients control it better during treatment, maybe the outcome will be better. That’s some of the research that I have personally been working on, but there is a lot of exciting work being done at Duke University Medical Center.”

Sarah Sammons, MD

Sarah Sammons, MD

Assistant Professor of Medicine, Duke University

“Some important questions that we want to answer in hormone receptor—positive, HER2-negative breast cancer in general are, ‘How are we going to turn an immunologically cold tumor, hot? How can we potentially make immunotherapy work in this population?’ There are a lot of preclinical data indicating that CDK4/6 inhibition may enhance immunogenicity. There are ongoing trials looking at adding immunotherapy to CDK4/6 inhibition, which is exciting. I believe we’re probably going to need to get a bit more elegant with how we pair immunotherapy with endocrine therapy and other immunotherapy agents or other targeted therapies. It’s going to take a lot of preclinical and translational work [to figure this out], and I’m doing a lot of that work at Duke University.”

Kelly E. Westbrook, MD

Kelly E. Westbrook, MD

Assistant Professor, Breast Cancer Program, Duke University School of Medicine

“The PATINA trial is an excellent option for patients who have ER-positive, HER2-positive breast cancer; it requires that patients have 6 to 8 cycles of chemotherapy and restaging scans that show no progression. That [stipulation] has caused a bit of a hiccup in terms of enrollment for the trial. The biggest thing is awareness that the trial is out there, because since first-line management for metastatic disease is pretty set in stone for the HER2-positive population, it often doesn’t get considered that there may be a trial to address how best to manage these patients. Therefore, for ER-positive patients who are receiving first-line chemotherapy, once they’ve had no progression, it’s the perfect time to then start their endocrine therapy. Also, this opens up the option for CDK4/6 inhibition, which we well know provides a significant advantage in the metastatic setting.

Then there is the AVIATOR trial, which is the trial examining immunotherapy in addition to HER2-targeted therapy. This trial is special in that there is no limitation to the number of previous lines of therapy that patients can have received. Really, the main exclusion criteria are that patients cannot have received vinorelbine, because that’s the chemotherapy backbone in that trial. They also cannot have received any prior immunotherapy.”