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Jul 24, 2019


Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Neelima Denduluri, a medical oncologist and Associate Chair of Breast Cancer for the US Oncology Network. Dr. Denduluri, welcome to the podcast.

Thank you for having me.

We're glad you're here. Today, we're talking about stand out poster presentations from the ASCO annual meeting that really stood out to you. Can you tell me a little bit what was interesting about this year's meeting?

I really enjoyed this year's ASCO because I thought there was a lot of focus on survivorship, prevention, and really focusing on our patients across the cancer care continuum. With regards to supportive care and what we do during treatment to make sure that our patients get through their treatments include reducing their risk of their blood counts dropping from chemotherapy.

A way that we often employ preoperative chemotherapy or adjuvant chemotherapy is in the dose-dense fashion, meaning that we give the chemotherapy at more rapid intervals. And one thing we've always wondered is, do we really need to use growth factor in a very commonly used regimen, the dose-dense AC paclitaxel regimen?

And interestingly, abstract 517 confirmed something that a lot of us have been doing in practice. And that is that for patients that don't have high risk of neutropenic fever, they don't need pegfilgrastim to reduce their risk of complications from paclitaxel being given in a dose-dense fashion.

I think that from a quality of life perspective for patients, that is dramatic. As we know, filgrastim and pegfilgrastim do cause arthralgias, low-grade fevers. And I thought that this was a step in the positive direction that we finally have data that suggests that we really don't need to use it in the paclitaxel portion in most of our patients. Additionally, it reduces the financial toxicity that our early breast cancer survivors have to go through as well.

Similarly, one thing that our patients struggle with is diarrhea with a drug that we use for HER2 positive breast cancer in the early breast cancer setting called neratinib. And one limiting issue with neratinib has always been the diarrhea.

The control study, which was abstract number 548, showed that those patients that we adequately recognized and educated them in saying, listen, diarrhea is an issue with neratinib, and we gave them prophylactic loperamide-- this trial also added budesonide and colestipol to loperamide prophylaxis for one to two cycles-- and found that it reduces the severity and duration of the diarrhea in those patients being treated with neratinib for their HER2 positive breast cancer.

So I thought both of these were really interesting in terms of moving the field forward in terms of tolerability. And one is to de-escalate care. And one is to escalate care.

So I want to shift gears a little bit to a subtype of breast cancer that we often focus on, triple negative breast cancer, to improve outcomes. We know that chemotherapy is paramount in this disease to reduce the risk of recurrence and improve disease free and overall survival in the early breast cancer setting. One thing that we don't know is who we need to add carboplatin to in addition to standard anthracycline and taxane-containing therapy to improve outcomes.

There have been multiple studies that have looked at this. And there are some confirmatory trials looking at this in the early breast cancer setting as well. One trial I want to highlight is the CALGB Alliance trial, which was presented in abstract 591. And what it showed was that regardless of treatment arm, pathologic complete response was associated with markedly better long-term outcomes. We also know that patients with any residual disease had significantly worse outcomes.

Now, when looking at the whole population, the addition of carboplatin to standard neoadjuvant chemotherapy did not improve long-term outcomes. Additionally, it led to omission of standard chemotherapy doses such as paclitaxel in the patients that were treated with carboplatin. We know that dose density and dose intensity are very important to long-term survivals in triple negative breast cancer.

So therefore, I thought that this was an interesting point that the authors made sure to make that the anthracycline and the taxane-containing part is very important. And if we add carboplatin, which is a very personalized decision, we need to make sure that the dose and that intensity and dose density are maintained because patients, they have worse outcomes. If the carboplatin is added, they have cytopenias, and we have to stop both the paclitaxel and the carboplatin.

Sounds like a lot of promising presentations this year. Any surprising results?

I don't think there were any surprising results. However, it was very gratifying, again, that certain subtypes of breast cancer are being looked at more closely. For example, abstract 546 looked at adjuvant enzalutamide for the treatment of early stage androgen receptor positive triple negative breast cancer. Growing research shows that triple negative breast cancer is a very heterogeneous disease.

And this trial nicely took patients that received their standard adjuvant therapy. And then these patients went on to receive enzalutamide, which targets the androgen receptor, for one year. And the authors showed that it was very tolerable. And the enzalutamide side may be the next step in how we improve outcomes for this special subtype of triple negative breast cancer.

Another abstract that was very interesting was abstract 552 that looked at the rates of osteonecrosis of the jaw in woman with breast cancer receiving bisphosphonates to prevent breast cancer metastases. We've always historically used bisphosphonates in the advanced breast cancer setting. However, we're increasingly using it in the early breast cancer setting.

And it was gratifying to see that the prevalence of the osteonecrosis of the jaw was very low and patients that, for example, had dentures, or plaques, or chemotherapy, or corticosteroid use were not at higher risk for osteonecrosis of the jaw. I thought this was reassuring for our highest risk early breast cancer patients.

Something else that we know from the breast cancer literature is that many of our patients have trouble adhering to adjuvant endocrine therapy. And that's very important in terms of improving outcomes. And there was a study, abstract 523, that showed that possibly patients that were in urban settings had lower adherence to adjuvant endocrine therapy.

Additionally, patients that were ages between 41 and 74 were more likely to adhere to their adjuvant endocrine therapy. That was reassuring. However, we as a community need to do better at improving tolerability. We know that acupuncture, duloxetine, yoga, regular exercise, possibly vitamin D may also improve tolerability to these medications.

One small feasibility abstract that I found interesting was 525, which enrolled 60 patients to receive tart cherry extract and showed that the patients that received the tart cherry extract actually had improved symptoms in terms of musculoskeletal symptoms from receiving this.


So I thought that's hopeful. And that's kind of surprising in terms of moving the field forward in terms of tolerability, coming up with novel ideas to try and improve adherence to these medications.

Absolutely. That leads in a little bit to my next question, which is, how do you talk to your patients about what you've seen and heard at the annual meeting?

One thing that our patients always want to know after the annual meeting when I come back is, what did you learn, and how does it affect me? And I tell them that there are three major themes. One is all of these stress to us that we as providers need to do a better job in terms of improving tolerability to these medications, that we are looking at this, and there's a lot of great research to help with us.

Second thing that we talk about is that the science is always dynamic. So what I may have said to you three years ago may change how I treat you now.

And then for our new breast cancer patients, one thing that has come up, I think, and has been reiterated is that we really need to make sure and incorporate our care in a multidisciplinary fashion not only with the surgeons, the radiation oncologists, which is a team we've always traditionally made sure to include, but also our primary care physicians, our gynecologists to improve tolerability.

That's great. What do you think is on the horizon for breast cancer care?

I think that this is a phrase that we often use but I think that further personalization of therapy. For example, in the last eight months, I think that the way that we treat, for example, early HER 2 positive breast cancer has transformed significantly in that majority of patients that are treated for early breast cancer, now, we meet them upfront before their surgery to discuss whether we should give chemotherapy up front with HER 2 targeted therapy, or should we give it to them after surgery?

And that's because we know that, those patients that don't achieve a pathologic complete response to HER 2 targeted therapy and chemotherapy, that we need to escalate their care, switch their care to other agents. So I think that there's going to be more of that in various subtypes of breast cancer in terms of more personalization.

That sounds great. It sounds like there's a lot of promise for the future of breast cancer care. Well, it's been a pleasure speaking with you. I wanted to thank you for being on our podcast today.

Thank you for having me.

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