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Biomarkers, PARP Inhibitors Vital for Personalized Treatment in Breast Cancer Subtypes

Jason Harris
Published: Wednesday, Aug 29, 2018

Banu K. Arun, MD

Banu K. Arun, MD

Developing predictive biomarkers will be key to treating patients with triple-negative breast cancer (TNBC), especially when choosing a targeted therapy, said Banu K. Arun, MD.

 during the meeting, Arun discussed the challenge of treating these patients, the value of genotyping, and what she hopes to see in future trial results.

OncLive: What were some key points of your lecture?

Arun: As you know, women with germline BRCA mutations mostly have high-grade cancers, especially BRCA1-related breast cancers. They have more triple-negative disease and more aggressive cancers. Recently, new approaches have been evaluated in these patients, including PARP inhibitors. I reviewed 2 very recently reported phase III studies looking at singleagent PARP inhibitors versus physician’s choice of therapy.

We don’t have any predictive biomarkers of response and we are just now beginning to do targeted therapy with immunotherapy and immunomodulation targeting the PI3K/AKT/mTOR pathway. We targeting the androgen receptor in TNBC. I reviewed the principles of these approaches but none of them are standard of care yet, unfortunately. We are still treating TNBC with standard therapies.

Has genotyping become more important since LOTUS was reported?

The LOTUS trial looked at an AKT inhibitor plus chemotherapy versus chemotherapy alone. The combination was significantly better than single-agent chemotherapy.

Genotyping is important, but these are the initial trials. We need to have validation. Biomarker assessment, overall, needs to be standardized, but we are headed in the right direction. Genotyping, not only to assess whether we would use this combination but for many agents targeting various subtypes in TNBC, will be important. However, we need more studies and more positive results.

Can you discuss immunogenicity in TNBC?

Immunotherapy is very interesting and very complicated, and it has become very exciting. When we started doing studies with PD-1/PD-L1 inhibitors, initial trials such as the KEYNOTE-012 trial showed some very promising results with an 18% response rate. However, the subsequent KEYNOTE-086 study in TNBC, unfortunately, showed only a 4.7% response rate.

Immunotherapy is not the answer as a single agent. We need to find the right subgroup, and perhaps the right combinations. Multiple studies are ongoing with combinations, either with chemotherapy or other targeted agents, including PARP inhibitors.

What trial results are you most looking forward to?

The trials that use biomarkers to help us identify which subgroup will benefit most from a given targeted intervention will be very important. Right now, we are still putting patients with a very heterogeneous group of cancers in the same bucket and trying to understand the results. When they don’t show promising results, we don’t know which subgroup might benefit more. Biomarker-driven, personalized, targeted therapy studies that show promising results—that’s what I’m looking for.

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View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
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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