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Old 06-26-2015, 12:00 PM   #1
Hopeful
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ASCO 2015 Recap: Dr. Kimberly Blackwell Circles Back to HER2/ER Breast Cancer—Part 1

Dr. Kimberly Blackwell, Professor of Medicine and Assistant Professor in Radiation Oncology at Duke and member of the PracticeUpdate Oncology Advisory Board, speaks with Dr. Jarushka Naidoo, an advanced fellow in medical oncology at Memorial Sloan Kettering Cancer Center, about what she considers to be important papers on HER2/ER breast cancer presented at this year’s ASCO Annual Meeting.


Dr. Naidoo: Dr. Blackwell, will you briefly discuss what you thought were the main highlights in the breast oncology world at ASCO this year?

Dr. Blackwell: This year’s ASCO was exciting in terms of breast cancer findings. I think that the PALOMA3 study has provided us with really meaningful data. PALOMA3 combined CDK inhibitors with fulvestrant, and we saw a significant improvement in progression-free survival (PFS).1 We also saw exciting data from our German colleagues about the use of TDM1 in the neoadjuvant setting.2

Role of immune checkpoint antibodies


Dr. Naidoo: What is your opinion of the prognostic role and potential therapeutic role for immune checkpoint antibodies in the treatment of breast cancer?

Dr. Blackwell: I think all of us are really excited about the use of immune checkpoint antibodies for the treatment of both metastatic and early-stage breast cancer. Although, melanoma, in particular, is further along in the immunotherapy world, I would argue that breast cancer also is pretty far along with the use of HER2-directed antibodies. Although these therapies are not directly impacting T cells, we believe that the main mechanism by which trastuzumab and pertuzumab work is by eliciting an ADCC (antibody dependent cellular cytotoxicity) response. I’m kind of proud that the breast cancer world, once again, may have led the way in the world of immunotherapy with the advent of HER2-targeted therapy.

There’s really no reason to believe that immunotherapies won’t hold the same promise in breast cancer as what we’ve already seen demonstrated in melanoma and non–small cell lung cancer. The breast cancer landscape is going to be a little bit more complicated because we have very active chemotherapeutic agents. I think a question that is going to have to be explored in order for these drugs to meet their full potential is how do we combine checkpoint inhibitors with chemotherapy? Or, should we combine checkpoint inhibitors with chemotherapy?

Most companies that are developing immune checkpoint inhibitors are launching very large clinical trials for women who are facing metastatic breast cancer. I would strongly encourage treating physicians to either go to www.clinicaltrials.gov or partner with a major cancer center where these trials are available as an option for their patients.


Role of antiangiogenics added to endocrine therapy

Dr. Naidoo: Dr. Maura Dickler and colleagues presented the results of a phase III trial of bevacizumab added to endocrine therapy in first-line treatment of patients with metastatic breast cancer, and shows a PFS benefit.3 What is your opinion of these data?

Dr. Blackwell: I don’t know what to do with it. The reality is that the study met its endpoint, and adding bevacizumab to an aromatase inhibitor significantly improved PFS with the toxicity profile we would expect with bevacizumab (hypertension, proteinuria, etc). The problem I face as a US practicing oncologist is that I can’t get the drug covered by payors and, therefore, although I would like to offer patients the advantage of this agent, unfortunately I cannot because of reimbursement issues.

The other component that makes this study difficult to put into perspective is that we now have data in an almost identical patient population for the aromatase inhibitors and the CDK inhibitors, which are approved in this space.4 So, for the time being, this is an example of a study that met its endpoint but does not change clinical practice, at least in the US, because the drug is not widely available or reimbursed.

I think that Dr. Dickler’s study will make a larger impact in countries where bevacizumab is actually available in patients with ER-positive metastatic breast cancer who have not received letrozole. I certainly would consider using bevacizumab on top of letrozole, especially in countries where bevacizumab is available, and the CDK inhibitors are not.

One would argue that almost all of the targeted agents that we’re now layering on top of endocrine therapy, whether the agent is a CDK inhibitor or, in this case, bevacizumab, may be associated with added toxicity as well as added cost. These things need to be discussed with the patient prior to initiating these therapies.

Dr. Naidoo: The use of antiangiogenic agents in the treatment of metastatic breast cancer is controversial and was the subject of an FDA-accelerated approval a few years ago, which was then revoked. What is your opinion of the role of antiangiogenic agents in breast cancer in general?

Dr. Blackwell: I think that antiangiogenic agents have demonstrated in almost all studies a statistically significant improvement in PFS in the absence of an overall survival (OS) benefit. They’ve all primarily been studied in a first-line setting, where we know that an OS benefit is tough to achieve. We know now that they’ve been utilized in thousands of breast cancer patients, if not over 10,000 patients with solid tumors. We know the toxicity of these agents.

There will be additional data regarding bevacizumab in combination with chemotherapy presented within the next year, and one would hope that these confirmatory, or secondary, studies will provide us clear guidance on how we should be using the antiangiogenics.

Hopeful
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