O'Shaughnessy Predicts Rapid Evolution in TNBC Landscape

Gina Columbus @ginacolumbusonc
Published Online: Monday, Feb 06, 2017

Joyce A. O’Shaughnessy, MD

Joyce A. O’Shaughnessy, MD

The triple-negative breast cancer (TNBC) pipeline is transforming, experts say, with the potential additions of immunotherapy and PARP inhibitors. These agents are being explored both as monotherapy and in combination regimens with standard chemotherapy options.

At the 2016 San Antonio Breast Cancer Symposium, treatment with pembrolizumab (Keytruda) continued to show a consistent durable benefit with an additional year of follow-up for heavily pretreated patients with recurrent PD-L1–positive TNBC, according to findings from the phase Ib KEYNOTE-012 trial.

At a median follow-up of 10.7 months, the median progression-free survival (PFS) was 1.9 months (95% CI, 1.6-5.5), and the 12-month PFS rate was 17.8%. The median overall survival (OS) was 11.3 months (95% CI, 5.3-18.2), and the 12-month OS rate was 47.1%.

Joyce A. O’Shaughnessy, MD, chair of Breast Cancer Research and the Celebrating Women Chair in Breast Cancer at Baylor-Sammons Cancer Center, Texas Oncology, and chair of The US Oncology Network, chaired the 2017 OncLive® State of the Science Summit on Treatment of Metastatic Breast Cancer. In an interview, she addressed the key issues in breast cancer discussed at the meeting and shared her expert insight on where TNBC treatment is headed based on recent findings.

OncLive: What are some of the key topics being discussed at this State of the Science Summit?

O'Shaughnessy: It is really nice to have the opportunity to have this summit right after SABCS to get everyone together to talk about the data. We’re talking about the estrogen receptor (ER)–positive patient—particularly focusing on the new data coming out with extended adjuvant endocrine therapy—as well as the premenopausal ER-positive patient and how to optimize that. Then, in metastatic breast cancer, there are new agents such as ribociclib. Of course, we have been using palbociclib (Ibrance). How do we sequence everolimus (Afinitor) for patients? There are a lot of new data in the ER-positive space.

In the HER2-positive space, we [discussed] new data emerging in the preoperative setting, as well as in the metastatic setting. There are new exciting data on using trastuzumab emtansine (T-DM1; Kadcyla) for brain metastases, for example.

In the curative setting, we are really focused on optimizing our chemotherapy at the moment and determining the role of anthracyclines and platinum-based agents. In the metastatic setting, what are the new agents coming along? What really holds promise? How will we understand the subsets of TNBC?

In the HER2-positive space, an exciting development hopefully will be coming up in 2017 with neratinib from the ExteNET study. That is the extended adjuvant therapy in the HER2-positive setting for patients who have already finished up their 1 year of adjuvant trastuzumab, and then patients might benefit from another year of the oral inhibitor neratinib.

That was a positive trial that showed a substantial improvement in outcomes, particularly in the ER-positive, HER2-positive patients who are at higher risk. That data will be going to the FDA very soon, [and we will find out] whether it will be approved for high-risk HER2-positive patients who still have substantial risk even after they have had their HER2-targeted therapy.

There is a lot of focus on new surgical and radiation therapy techniques with local controlled data. This is always a moving field because we are going toward less surgery, or more preoperative therapy. How do we optimize surgery and radiation therapy for patients who are getting sentinel biopsy or preoperative therapy?

There are also some novel diagnostics and new molecular profiles being used in the ER-positive patient. Who needs chemotherapy, and who does not? What about some of the new assays to try to understand who will benefit from extended adjuvant endocrine therapy?

How about about some of these new mutations we're finding, such as…the ESR1 mutation, using circulating tumor DNA? Is that at all clinically useful at this time? It’s really covering local control, ER-positive, HER2-positive, triple-negative, and some of the novel diagnostics. We are really covering the waterfront.

Your talk specifically focused on TNBC. What is important to note in this area?

TNBC is in rapid evolution, and we are going to see some stunning progress in the next few years, fortunately. What are the current data we have with carboplatin or platinum-based agents? What about capecitabine in high-risk patients? Our chemotherapy agents are old friends, but are they really useful in the curative setting?




View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Clinical Vignette Series: 33rd Annual Miami Breast Cancer Conference®May 18, 20172.0
Medical Crossfire®: Integrating CDK4/6 Inhibitors into the Management of Breast CancersMay 26, 20171.5
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