Top Breast Cancer Oncologists Highlight Their Ongoing Research

At the 2019 OncLive^® State of the Science Summit™ on Breast Cancer, experts from Emory University School of Medicine, Massachusetts General Hospital, and Hospital of the University of Pennsylvania, highlighted the exciting research being conducted at their respective institutions.

Jane Meisel, MD

Jane Meisel, MD

Assistant Professor, Department of Hematology and Medical Oncology and Department of Gynecology & Obstetrics, Winship Cancer Institute, Emory University School of Medicine

“One of the big questions that remains in metastatic estrogen receptor (ER)—positive breast cancer is what to do after progression on CDK4/6 inhibitors given in the first-line setting. We have recently opened the phase II PACE trial, which is enrolling women after progression on an aromatase inhibitor plus a CDK4/6 inhibitor and is randomizing them to 1 of 3 arms: fulvestrant (Faslodex), fulvestrant plus palbociclib (Ibrance), or fulvestrant/palbociclib/avelumab (Bavencio).

This trial hopes to assess the value of continuing CDK4/6 inhibition while switching the endocrine backbone, and also to better understand the possible value of immunotherapy along with these combinations. Moreover, there are several correlative studies built into this trial which will hopefully provide an early assessment of which groups might benefit from which approaches and why.

We have also recently opened the I-SPY 2 trial, an ambitious neoadjuvant study that is evaluating novel agents combined with traditional neoadjuvant therapies for high-risk, early-stage, ER-positive, HER2-positive, and triple-negative breast cancer (TNBC). The success of neoadjuvant pembrolizumab (Keytruda) combined with paclitaxel that led to KEYNOTE-522 was first highlighted in the I-SPY results presented at [a prior ASCO Annual Meeting]. We are excited to contribute to this potentially practice-changing study and to offer access to novel agents to the women of Atlanta, and our surrounding communities.”

Keerthi Gogineni, MD, MSHP

Keerthi Gogineni, MD, MSHP

Assistant Professor, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine

“One of the goals right now that we’re hoping to accomplish is to incorporate immunotherapy into the HER2-positive treatment setting. One of the ways that we are doing that is by partnering with Moffitt [Cancer Center] and the University of Washington to offer a vaccine approach for patients who have residual disease [after having been] treated for HER2-positive disease. We’re looking at these patients to see if giving them a vaccine that is either based on their residual tumor or a peptide is going to help increase surveillance and lower their risk of recurrence later.”

Manali Bhave, MD

Manali Bhave, MD

Assistant Professor, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine

“We have many clinical trials that are coming to Emory University School of Medicine, including phase I, phase II, and phase III trials. We had the HER2CLIMB trial, which was a tucatinib-based trial for HER2-positive metastatic breast cancer—a heavily pretreated population. One of the exciting results that came out of that was the central nervous system (CNS) response seen with tucatinib, which was about 42%. What we’re looking for now, in some of our novel therapies, is enhanced responses and improvement in CNS disease, because unfortunately, that appears to be a place where we’re lacking in terms of treatment for patients with HER2-positive metastatic breast cancer.

We have other trials that are looking at combinations of CDK4/6 inhibitors along with endocrine therapy and anti—HER2-directed therapy for patients with triple-positive metastatic disease. We had a trial called the PATINA trial at Emory University School of Medicine, which was open, and soon, we’ll get more of those trials [at our institution]. We have some very exciting combinations that we’ll bring to our patients with metastatic breast cancer.”

Aditya Bardia, MD, MPH

Aditya Bardia, MD, MPH

Assistant Professor of Medicine, Harvard Medical School, Attending Physician, Medical Oncology, Massachusetts General Hospital

“I would like to highlight three [research areas] related to the management of TNBC that we’re really excited about at our institution. The first is, [we are working on] building on [the success seen with] combination therapies. We have been involved in the development of sacituzumab govitecan, the antibody-drug conjugate for metastatic TNBC. [With that agent, we are] seeing a response rate of over 30%, but I want a response rate of 50%, 70%, or even 80%. I want to push that bar.

It’s important to understand that those patients who respond very well to single-agent therapy as well as those who had some response [and working to improve] that response. For the latter category, we would need combination therapy. [To this end], we are working in the laboratory as well as the clinic to develop these combination therapies. I’m particularly excited about the combination of sacituzumab govitecan with a PARP inhibitor because I feel that could potentially push the boundary in terms of improving survival.

The second thing that we are excited about at our institution is [our work being done to better] understand racial disparities. We have established a collaboration with Boston Medical Center to understand the issue of racial disparities in TNBC. From a biologic perspective, we want to understand why [more] African Americans have TNBC as opposed to hormone­ receptor (HR)—positive breast cancer, which is more common in the Caucasian population.

The third [area of research has to do with] circulating tumor cells (CTCs). Patients who have TNBC have a different biology as opposed to [those with] HR­-positive breast cancer. If we can isolate the tumor cells and generate models, we can then develop specific combination therapies that are targeted to that particular phenotype.

As such, in the lab, we have been interested in developing ex vivo models from patients’ CTCs and doing drug sensitivity experiments. If we can really [identify] a very important combination, that could potentially then be applied back to the patient. It’s very early research, but the promise is along the lines of [what is done in] infectious diseases. There’s an infection, you do the blood culture, identify that a bug is sensitive to an antibiotic, and then give that antibiotic to the patient. Here, we culture CTCs, identify [what this] individual would be sensitive [to] in terms of drug combinations, and then apply that [treatment] back to the patient. [This work is] not ready for prime time, but it could potentially be very promising.”

Payal D. Shah, MD

Payal D. Shah, MD

Assistant Professor of Medicine, Hospital of the University of Pennsylvania

“One clinical trial that we will soon be opening is examining olaparib (Lynparza) in combination with palbociclib and fulvestrant for patients with BRCA-associated HR-positive metastatic breast cancer. The question is, ‘Will this combination be tolerable, noting that there are some overlapping toxicities?’ The second question is, ‘Will this combination be effective, noting that olaparib is effective in these cancers because it targets DNA repair and palbociclib and fulvestrant are effective in these cancers as well?’ Also, will the combination simultaneously target two drivers of tumor growth and result in better outcomes for our patients? I’m really excited about that trial.”