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TNBC Remains Challenging Arena, But Emerging Therapies Show Promise

Gina Columbus @ginacolumbusonc
Published: Thursday, May 25, 2017

Kari B. Wisinski, MD

Kari B. Wisinski, MD

While chemotherapy regimens remain the standard approach for patients with triple-negative breast cancer (TNBC), investigators have been exploring other agents within this heterogeneous disease, including PARP inhibitors and checkpoint inhibitors.

Some TNBCs have demonstrated sensitivity to immunotherapy, specifically in patients with high levels of PD-L1 expression. Most recently, phase Ib/II findings demonstrated that the combination of eribulin (Halaven) and pembrolizumab (Keytruda) had a promising objective response rate at 41.2% for untreated patients with metastatic TNBC.1

At the 2017 ASCO Annual Meeting, preliminary results will be presented from the phase II KEYNOTE-086 trial cohort B, which is looking at pembrolizumab in the first-line setting for patients with PD-L1–positive metastatic TNBC.2

Moreover, PARP inhibition is currently being studied in a phase I trial in patients with unresectable metastatic solid tumors, including TNBC (NCT02317874). In the study, patients are treated with the PARP inhibitor talazoparib plus carboplatin/paclitaxel, and maximum-tolerated dose and recommended phase II dose are the primary endpoints.

In an interview during the 2017 OncLive State of the Science Summit on Metastatic Breast Cancer, Kari B. Wisinski, MD, an associate professor of medicine at University of Wisconsin School of Medicine and Public Health, discussed the evolving but challenging field of TNBC and what therapies are moving through the pipeline in TNBC and other breast cancer subtypes.

OncLive: You lectured on TNBC and emerging therapies at the meeting. What can you share about the TNBC paradigm?

Wisinski: The key thing I talked about is how this is a different type of disease. Particularly, this affects younger women and African-American women, and it has an association with BRCA1 carriers. Then, I transitioned to talk more about the role of chemotherapy—particularly the ABC study that came out last year at the 2016 ASCO Annual Meeting, which supported the use of anthracyclines in TNBC for early-stage adjuvant therapy. 

I also talked about carboplatin and its role in neoadjuvant therapy for TNBC, some of the current data, the limitations of that data, and where we currently stand. 

Can you discuss the ABC study and what it demonstrated?

The ABC study was a gathering of a few different studies that looked at anthracycline-containing chemotherapies with taxanes versus docetaxel and cyclophosphamide chemotherapy for 6 cycles. The question was, can we avoid anthracyclines safely in early stage breast cancer? The data very clearly showed that anthracyclines have a role, particularly in TNBC. 

What are your thoughts on the buzz of immunotherapy surrounding TNBC?

TNBC is not 1 disease and we know that there are multiple different subtypes of TNBC. That really ties into the immunotherapy question, because there has been a portion of women with TNBC who do seem to benefit from immunotherapy. But, we don’t have the ability to select which patients those are. It is very possible that it might link back to some of those subtypes of patients with TNBC, or some of the mutational burden of these tumors. 

Please discuss sacituzumab govitecan (IMMU-132) and the role of chemotherapy in TNBC?

Well, sacituzumab govitecan is still a chemotherapy. It is an antibody-drug conjugate that is targeting chemotherapy to the cancer cells, based on the expression of Trop-2 in TNBC. It is an interesting agent, but it does need to be validated prospectively in larger studies.

Are we going to move away from chemotherapy in TNBC? It is going to probably depend on the subtype. There will be some TNBCs that potentially have a very good prognosis. There are some data with tumor-infiltrating lymphocytes (TILs)—that TNBC with high TILs may have a very good prognosis. There are some questions about how we treat those. Do we need chemotherapy or not? We are not there yet to make that decision, but it will be interesting. 

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Community Practice Connections™: How Do We Leverage PARP Inhibition Strategies in the Contemporary Treatment of Breast Cancer?May 31, 20191.5
Community Practice Connections™: A Better Way to Stop Pain: Paths Toward Responsible Postsurgical Pain Management for Patients With Breast CancerMay 31, 20191.5
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