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Neelima Denduluri

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Dr. Neelima Denduluri, a medical oncologist at Virginia Cancer Specialists and Associate Chair of the Breast Cancer Research for the US Oncology Network, discusses key abstracts in the breast cancer field that were featured at the ASCO20 Virtual Scientific Program.   Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Joining me today is Dr. Neelima Denduluri, a medical oncologist at Virginia Cancer Specialists and Associate Chair of Breast Cancer Research for the US Oncology Network. Dr. Denduluri serves on the editorial board of the ASCO Daily News, and will highlight key abstracts that were featured at the ASCO20 Virtual Scientific Program.   Dr. Denduluri has received institutional research funding from Amgen, Novartis, Genentech, Eli Lilly, Pfizer, Daiichi Sankyo, Seattle Genetics and Immunomedics. Full disclosures relating to all Daily News podcasts can be found on our episode pages. Dr. Denduluri, it's great to have you on the podcast today.   Dr. Neelima Denduluri: Thank you, Geraldine, for asking me to participate on the podcast.   ASCO Daily News: Let's start with advanced breast cancer. Can you tell us about the key abstracts that address this patient population?   Dr. Neelima Denduluri: Absolutely. So this year's ASCO was filled with many rich advancements across the therapeutic, diagnostic, and symptom management spectrum, which is always wonderful when we're trying to treat our patients adequately. In advanced breast cancer, one abstract that generated significant interest is whether surgery improves outcomes in patients that present with advanced breast cancer.   Generally, the paradigm in advanced breast cancer is to give systemic therapy. We've always wondered, does taking out the local site of disease or the primary tumor, in terms of the breast tumor and lymph nodes, and possibly giving radiation, does that improve outcomes in advanced breast cancer? Well, the late-breaking abstract 2 (LBA2), presented by Dr. Khan, looked at women or men who presented with stage IV de novo breast cancer. And these patients obviously started their appropriate systemic therapy based on the subtype of breast cancer.   And these patients, after three to six months, were randomized to continue the systemic therapy or stop their systemic therapy for local management before resuming their systemic therapy. And what the study showed is that those patients that did receive local therapy did not have an improvement in survival compared with those patients that did not receive local therapy to their breasts and/or lymph nodes. So I think that was an excellent lesson for all of us. And how it guides our management is to say that the vast majority of our patients with advanced breast cancer do not need to undergo surgery to improve outcomes. Now, having said that, about 25% of patients that did not have any local therapy did have some progression. And so for those patients, despite no improvement in long-term quality of life, it is something that we should consider and talk about with them. Especially if that is the only site of disease that is progressing, should we go ahead and give them some palliation in terms of symptoms in the short term.   The most common subtype of advanced breast cancer that we treat is hormone receptor positive, HER2 negative breast cancer. There are data that have been previously presented that show that fulvestrant, which is an injectable selective estrogen receptor downgrader, is possibly superior to aromatase inhibitors. So one trial evaluated this concept, but in the face of CDK4/6 inhibition. CDK4/6 inhibitors have become the mainstay of therapy in advanced hormone receptor positive, HER2 negative breast cancer. What abstract 1007, or the PARSIFAL trial, looked at was is fulvestrant and a CDK4/6 inhibitor superior to an aromatase inhibitor and CDK4/6 inhibitor. And what they showed is that, in advanced breast cancer, fulvestrant was not superior to an aromatase inhibitor when given in combination with CDK4/6 inhibition. And this is something that I think was reassuring to patients, especially if they have to come in to the clinic to receive an injection.   What will be interesting going forward is how do selective estrogen receptor downgraders that are oral come into play, and how do they compare with fulvestrant or how do they compare with aromatase inhibitors. So that was something that was quite reassuring, that we can give aromatase inhibitors with CDK4/6 inhibitors without compromising efficacy in patients with advanced breast cancer.   Another trial that generated some excitement for our patients and therapeutic options is the BYLieve trial, or abstract 1006. As I stated earlier, the mainstay of therapy for those patients with advanced breast cancer that's hormone receptor positive and HER2 negative is some type of endocrine partner, whether it be tamoxifen, fulvestrant, or an aromatase inhibitor and a CDK4/6 inhibitor. Mainly, it's an aromatase inhibitor and a CDK4/6 inhibitor. So for those patients that progress on that regimen, what do we do next is something that comes up.   We know that up to 40% of patients with advanced breast cancer that's hormone receptor positive and HER2 negative have PI3-kinase mutations, and alpha-specific PI3-kinase inhibitor that has shown to improve outcomes in patients with advanced breast cancer that have PI3-kinase mutations. What the BYLieve trial looked at was how about after CDK4/6 inhibition.   And what it showed is that patients that received CDK4/6 inhibition and fulvestrant and alpelisib did have about a 50% chance of not progressing at six months. And there was about a seven-month progression-free survival benefit in these patients. The toxicities that we know of with alpelisib include rash, diarrhea, and hyperglycemia. And those side effects were reported less than in the SOLAR-1 trial.   So we know that, in this group of patients, we really do need to monitor their blood sugars, give them prophylactic antihistamines, and also counsel them on adequate anti-diarrheal management. So the BYLieve trial helped us with two concepts. One is, after CDK4/6 inhibition, in those patients with PI3-kinase mutations, yes, there is a role for alpelisib. And the second thing is that we're doing a better job, while we can't do cross-trial comparisons, of improving the quality of life and symptoms that arise from alpelisib, including the rash, the diarrhea, and the hyperglycemia.   Another trial that was very exciting, shifting gears, is the HER2CLIMB trial. And that was abstract 1005. We knew from December that tucatinib improves outcomes when added to trastuzumab and capecitabine in patients with advanced HER2 positive breast cancer. We also knew that it does improve survival irrespective of brain metastases, and brain metastases that might have been progressing.   What this analysis of the HER2CLIMB showed was that the patients that received tucatinib did have an improved survival benefit compared with trastuzumab and capecitabine of six months. Additionally, the response rate solely in the central nervous system was 41% on the tucatinib arm versus 23% on the arm that received capecitabine and trastuzumab alone. So these were really exciting data because we do know that about 50% of patients with advanced stage IV breast cancer that's HER2 positive do eventually develop brain metastases.   So while we know that tucatinib, in addition to trastuzumab and capecitabine, does improve survival irrespective of brain metastases, we know now that those patients with progressing brain metastases do have an improved outcome when tucatinib is added. The side effects that we have to monitor for are diarrhea and liver function abnormalities, of course.   Shifting gears a little bit more is the immunotherapy trial in triple-negative breast cancer. And that is abstract 1000. So over the past 12 to 18 months, we've seen data from the IMpassion130 trial, which showed that patients who had PD-L1 positivity in their immune cells did derive benefit when atezolizumab was added to nab-paclitaxel, and it did improve outcomes.   Now, this trial, the KEYNOTE-355 trial, looked at patients that were untreated for their advanced breast cancer. And these patients were randomized to paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin chemotherapy with pembrolizumab or without pembrolizumab. And what was noted is those patients that had a combined positive score of PD-L1 greater than or equal to 10 derived about a four-month progression-free survival benefit if they received pembrolizumab.   Now, we have two trials, the IMpassion trial and the KEYNOTE trial, that show that patients with some element of PD-L1 expression, whether it's the immune cells, as evidenced by the IMpassion trial, or the combined positive score of PD-L1, as was evaluated in the KEYNOTE trial, did have significantly better outcomes if immunotherapy was incorporated as first-line treatment for their triple-negative breast cancer.   There are questions, though, that we have to answer, in what is the optimal measurement to predict response to immunotherapy in the triple-negative breast cancer setting, and also what is the optimal cut point that we should use to say whether we should employ immunotherapy. However, it was another advancement for an unmet need, which is triple-negative breast cancer.   One thing we know in advanced breast cancer, whether it's because of PI3-kinase mutations, whether it's measuring PD-L1, that we need to do testing beyond estrogen receptor, progesterone receptor, and HER2. We're increasingly utilizing genomic and germline testing to see if we can give more personalized therapy to our patients. 1002 looked at the effectiveness of patients with BRCA mutations that were somatic, as well as patients with germline mutations, including PALB2, and they found that olaparib did improve outcomes in patients with somatic BRCA mutations, as well as those patients that harbored PALB2 mutations. So I think that this is another reason for us to make sure that we are sending our patients for germline testing in the advanced breast cancer setting, as well as to make sure that we're looking for somatic mutations that we can target.   ASCO Daily News: What are your key takeaways from the studies on early breast cancer?   Dr. Neelima Denduluri: Thanks for asking that question. As I said earlier, there are many advancements, but one that I want to highlight is abstract 501. We know that anthracyclines have improved survival in breast cancer over the last several decades. However, we also know that HER2-targeted therapy using trastuzumab, pertuzumab, and now TDM1 has significantly improved outcomes in early breast cancer. So we've never known whether we truly need to give anthracyclines in the face of effective HER2-targeted therapy.   The TRAIN-2 trial, which is abstract 501, evaluated whether anthracyclines improve outcomes when there is optimal HER2-targeted therapy. And the answer is no, it did not. So I think that's very promising. And potentially, what we'll be able to do is to decrease cardiotoxicity, as well as treatment-related leukemias and myelodysplasia, possibly, in terms of reducing the risk of those by omitting anthracyclines in the early HER2 breast cancer setting.   Another abstract that I want to highlight is 507, which was looking at the role of adjuvant capecitabine in a metronomic fashion, meaning lower doses and giving it for a longer period of time, in those patients with triple-negative breast cancer. Just to give a quick historical background, we know from the CREATE-X trial that those patients that received preoperative therapy with third-generation chemotherapy and had residual disease at the time of surgery, those patients did benefit from the addition of capecitabine as part of their adjuvant treatment, compared with no adjuvant treatment.   So these are further data that we have further elucidating the role of capecitabine, primarily in the triple-negative breast cancer setting. And we did see that there was an improved outcome in terms of disease-free survival in these patients with anatomic stage I to III triple-negative breast cancer, and they did benefit from the addition of capecitabine.   Also, two side effects that we worry about with capecitabine are diarrhea and hand-foot syndrome. And they seem to be more manageable with this lower dose of capecitabine compared with the traditional 2,500 mgs per meter squared twice a day that was approved initially with capecitabine or that was used in CREATE-X.   ASCO Daily News: Dr. Denduluri, are there any new advancements in supportive care and symptom management?   Dr. Neelima Denduluri: So Geraldine, we know that a geriatric assessment is very important when we treat our patients that are elderly. Abstract 12009 performed a geriatric assessment on patients that had stage III or IV cancer and were aged 70 or older. And once they performed that geriatric assessment, they sent the treating oncologist the geriatric assessment and guided recommendations to improve their tolerance to therapy, potentially. And what they found is that it reduced clinically graded grade III to V toxicities significantly by providing this geriatric assessment. And also, it didn't lower survival.   So I thought that this was really nice prospective data that shows that we should be performing a geriatric assessment, and what we find, we should make sure to support our patients better based on the findings. And this improves our patients' tolerability to therapy, and it does not decrease their survival. So I thought that that was a very uplifting trial. We have a lot of programs around the country that are saying how best do we support our geriatric population, and this was a good step in the right direction.   ASCO Daily News: Absolutely. Is there anything else you'd like to add today? Any other abstracts that we should know about?   Dr. Neelima Denduluri: A couple of other things that we talk about quite a bit in our clinic is disparities. And abstract 1080 found that those patients with triple-negative breast cancer were continuing to receive non-guideline-adherent care when it was compared to their Caucasian population compared with the black population. So I think that this underscores that we really need to make sure that we address the disparities in cancer care.   Cancer survivorship is very important. One thing that patients complain about is insomnia. Abstract 12005 showed that yoga, cognitive behavioral therapy, and survivorship health education really improved insomnia in cancer survivors. So again, when we look at taking care of patients, we really need to look at the whole spectrum. And while we have excellent drugs and drug development that is improving outcomes, we also need to make sure that disparities, financial toxicity, survivorship are addressed. And therefore, I thought that this ASCO did a great job of looking at those issues, as well as drug development.   ASCO Daily News: Absolutely. Well, thank you, Dr. Denduluri, for sharing your insights with us today on these promising new developments in the breast cancer field.   Dr. Neelima Denduluri: Thank you, Geraldine.   ASCO Daily News: And thanks to our listeners for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us on Apple Podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   COI Disclosure:  Dr. Neelima Denduluri Consulting/Advisory Role: Daiichi Sankyo Research Funding: Amgen, Novartis, Genentech, Lilly, Pfizer, Immunomedics

Dr. Neelima Denduluri, a medical oncologist at Virginia Cancer Specialists and Associate Chair of the Breast Cancer Research for the US Oncology Network, discusses key abstracts in the breast cancer field that were featured at the ASCO20 Virtual Scientific Program. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Joining me today is Dr. Neelima Denduluri, a medical oncologist at Virginia Cancer Specialists and Associate Chair of Breast Cancer Research for the US Oncology Network. Dr. Denduluri serves on the editorial board of the ASCO Daily News, and will highlight key abstracts that were featured at the ASCO20 Virtual Scientific Program. Dr. Denduluri has received institutional research funding from Amgen, Novartis, Genentech, Eli Lilly, Pfizer, Daiichi Sankyo, Seattle Genetics and Immunomedics. Full disclosures relating to all Daily News podcasts can be found on our episode pages. Dr. Denduluri, it's great to have you on the podcast today. Dr. Neelima Denduluri: Thank you, Geraldine, for asking me to participate on the podcast. ASCO Daily News: Let's start with advanced breast cancer. Can you tell us about the key abstracts that address this patient population? Dr. Neelima Denduluri: Absolutely. So this year's ASCO was filled with many rich advancements across the therapeutic, diagnostic, and symptom management spectrum, which is always wonderful when we're trying to treat our patients adequately. In advanced breast cancer, one abstract that generated significant interest is whether surgery improves outcomes in patients that present with advanced breast cancer. Generally, the paradigm in advanced breast cancer is to give systemic therapy. We've always wondered, does taking out the local site of disease or the primary tumor, in terms of the breast tumor and lymph nodes, and possibly giving radiation, does that improve outcomes in advanced breast cancer? Well, the late-breaking abstract 2 (LBA2), presented by Dr. Khan, looked at women or men who presented with stage IV de novo breast cancer. And these patients obviously started their appropriate systemic therapy based on the subtype of breast cancer. And these patients, after three to six months, were randomized to continue the systemic therapy or stop their systemic therapy for local management before resuming their systemic therapy. And what the study showed is that those patients that did receive local therapy did not have an improvement in survival compared with those patients that did not receive local therapy to their breasts and/or lymph nodes. So I think that was an excellent lesson for all of us. And how it guides our management is to say that the vast majority of our patients with advanced breast cancer do not need to undergo surgery to improve outcomes. Now, having said that, about 25% of patients that did not have any local therapy did have some progression. And so for those patients, despite no improvement in long-term quality of life, it is something that we should consider and talk about with them. Especially if that is the only site of disease that is progressing, should we go ahead and give them some palliation in terms of symptoms in the short term. The most common subtype of advanced breast cancer that we treat is hormone receptor positive, HER2 negative breast cancer. There are data that have been previously presented that show that fulvestrant, which is an injectable selective estrogen receptor downgrader, is possibly superior to aromatase inhibitors. So one trial evaluated this concept, but in the face of CDK4/6 inhibition. CDK4/6 inhibitors have become the mainstay of therapy in advanced hormone receptor positive, HER2 negative breast cancer. What abstract 1007, or the PARSIFAL trial, looked at was is fulvestrant and a CDK4/6 inhibitor superior to an aromatase inhibitor and CDK4/6 inhibitor. And what they showed is that, in advanced breast cancer, fulvestrant was not superior to an aromatase inhibitor when given in combination with CDK4/6 inhibition. And this is something that I think was reassuring to patients, especially if they have to come in to the clinic to receive an injection. What will be interesting going forward is how do selective estrogen receptor downgraders that are oral come into play, and how do they compare with fulvestrant or how do they compare with aromatase inhibitors. So that was something that was quite reassuring, that we can give aromatase inhibitors with CDK4/6 inhibitors without compromising efficacy in patients with advanced breast cancer. Another trial that generated some excitement for our patients and therapeutic options is the BYLieve trial, or abstract 1006. As I stated earlier, the mainstay of therapy for those patients with advanced breast cancer that's hormone receptor positive and HER2 negative is some type of endocrine partner, whether it be tamoxifen, fulvestrant, or an aromatase inhibitor and a CDK4/6 inhibitor. Mainly, it's an aromatase inhibitor and a CDK4/6 inhibitor. So for those patients that progress on that regimen, what do we do next is something that comes up. We know that up to 40% of patients with advanced breast cancer that's hormone receptor positive and HER2 negative have PI3-kinase mutations, and alpha-specific PI3-kinase inhibitor that has shown to improve outcomes in patients with advanced breast cancer that have PI3-kinase mutations. What the BYLieve trial looked at was how about after CDK4/6 inhibition. And what it showed is that patients that received CDK4/6 inhibition and fulvestrant and alpelisib did have about a 50% chance of not progressing at six months. And there was about a seven-month progression-free survival benefit in these patients. The toxicities that we know of with alpelisib include rash, diarrhea, and hyperglycemia. And those side effects were reported less than in the SOLAR-1 trial. So we know that, in this group of patients, we really do need to monitor their blood sugars, give them prophylactic antihistamines, and also counsel them on adequate anti-diarrheal management. So the BYLieve trial helped us with two concepts. One is, after CDK4/6 inhibition, in those patients with PI3-kinase mutations, yes, there is a role for alpelisib. And the second thing is that we're doing a better job, while we can't do cross-trial comparisons, of improving the quality of life and symptoms that arise from alpelisib, including the rash, the diarrhea, and the hyperglycemia. Another trial that was very exciting, shifting gears, is the HER2CLIMB trial. And that was abstract 1005. We knew from December that tucatinib improves outcomes when added to trastuzumab and capecitabine in patients with advanced HER2 positive breast cancer. We also knew that it does improve survival irrespective of brain metastases, and brain metastases that might have been progressing. What this analysis of the HER2CLIMB showed was that the patients that received tucatinib did have an improved survival benefit compared with trastuzumab and capecitabine of six months. Additionally, the response rate solely in the central nervous system was 41% on the tucatinib arm versus 23% on the arm that received capecitabine and trastuzumab alone. So these were really exciting data because we do know that about 50% of patients with advanced stage IV breast cancer that's HER2 positive do eventually develop brain metastases. So while we know that tucatinib, in addition to trastuzumab and capecitabine, does improve survival irrespective of brain metastases, we know now that those patients with progressing brain metastases do have an improved outcome when tucatinib is added. The side effects that we have to monitor for are diarrhea and liver function abnormalities, of course. Shifting gears a little bit more is the immunotherapy trial in triple-negative breast cancer. And that is abstract 1000. So over the past 12 to 18 months, we've seen data from the IMpassion130 trial, which showed that patients who had PD-L1 positivity in their immune cells did derive benefit when atezolizumab was added to nab-paclitaxel, and it did improve outcomes. Now, this trial, the KEYNOTE-355 trial, looked at patients that were untreated for their advanced breast cancer. And these patients were randomized to paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin chemotherapy with pembrolizumab or without pembrolizumab. And what was noted is those patients that had a combined positive score of PD-L1 greater than or equal to 10 derived about a four-month progression-free survival benefit if they received pembrolizumab. Now, we have two trials, the IMpassion trial and the KEYNOTE trial, that show that patients with some element of PD-L1 expression, whether it's the immune cells, as evidenced by the IMpassion trial, or the combined positive score of PD-L1, as was evaluated in the KEYNOTE trial, did have significantly better outcomes if immunotherapy was incorporated as first-line treatment for their triple-negative breast cancer. There are questions, though, that we have to answer, in what is the optimal measurement to predict response to immunotherapy in the triple-negative breast cancer setting, and also what is the optimal cut point that we should use to say whether we should employ immunotherapy. However, it was another advancement for an unmet need, which is triple-negative breast cancer. One thing we know in advanced breast cancer, whether it's because of PI3-kinase mutations, whether it's measuring PD-L1, that we need to do testing beyond estrogen receptor, progesterone receptor, and HER2. We're increasingly utilizing genomic and germline testing to see if we can give more personalized therapy to our patients. 1002 looked at the effectiveness of patients with BRCA mutations that were somatic, as well as patients with germline mutations, including PALB2, and they found that olaparib did improve outcomes in patients with somatic BRCA mutations, as well as those patients that harbored PALB2 mutations. So I think that this is another reason for us to make sure that we are sending our patients for germline testing in the advanced breast cancer setting, as well as to make sure that we're looking for somatic mutations that we can target. ASCO Daily News: What are your key takeaways from the studies on early breast cancer? Dr. Neelima Denduluri: Thanks for asking that question. As I said earlier, there are many advancements, but one that I want to highlight is abstract 501. We know that anthracyclines have improved survival in breast cancer over the last several decades. However, we also know that HER2-targeted therapy using trastuzumab, pertuzumab, and now TDM1 has significantly improved outcomes in early breast cancer. So we've never known whether we truly need to give anthracyclines in the face of effective HER2-targeted therapy. The TRAIN-2 trial, which is abstract 501, evaluated whether anthracyclines improve outcomes when there is optimal HER2-targeted therapy. And the answer is no, it did not. So I think that's very promising. And potentially, what we'll be able to do is to decrease cardiotoxicity, as well as treatment-related leukemias and myelodysplasia, possibly, in terms of reducing the risk of those by omitting anthracyclines in the early HER2 breast cancer setting. Another abstract that I want to highlight is 507, which was looking at the role of adjuvant capecitabine in a metronomic fashion, meaning lower doses and giving it for a longer period of time, in those patients with triple-negative breast cancer. Just to give a quick historical background, we know from the CREATE-X trial that those patients that received preoperative therapy with third-generation chemotherapy and had residual disease at the time of surgery, those patients did benefit from the addition of capecitabine as part of their adjuvant treatment, compared with no adjuvant treatment. So these are further data that we have further elucidating the role of capecitabine, primarily in the triple-negative breast cancer setting. And we did see that there was an improved outcome in terms of disease-free survival in these patients with anatomic stage I to III triple-negative breast cancer, and they did benefit from the addition of capecitabine. Also, two side effects that we worry about with capecitabine are diarrhea and hand-foot syndrome. And they seem to be more manageable with this lower dose of capecitabine compared with the traditional 2,500 mgs per meter squared twice a day that was approved initially with capecitabine or that was used in CREATE-X. ASCO Daily News: Dr. Denduluri, are there any new advancements in supportive care and symptom management? Dr. Neelima Denduluri: So Geraldine, we know that a geriatric assessment is very important when we treat our patients that are elderly. Abstract 12009 performed a geriatric assessment on patients that had stage III or IV cancer and were aged 70 or older. And once they performed that geriatric assessment, they sent the treating oncologist the geriatric assessment and guided recommendations to improve their tolerance to therapy, potentially. And what they found is that it reduced clinically graded grade III to V toxicities significantly by providing this geriatric assessment. And also, it didn't lower survival. So I thought that this was really nice prospective data that shows that we should be performing a geriatric assessment, and what we find, we should make sure to support our patients better based on the findings. And this improves our patients' tolerability to therapy, and it does not decrease their survival. So I thought that that was a very uplifting trial. We have a lot of programs around the country that are saying how best do we support our geriatric population, and this was a good step in the right direction. ASCO Daily News: Absolutely. Is there anything else you'd like to add today? Any other abstracts that we should know about? Dr. Neelima Denduluri: A couple of other things that we talk about quite a bit in our clinic is disparities. And abstract 1080 found that those patients with triple-negative breast cancer were continuing to receive non-guideline-adherent care when it was compared to their Caucasian population compared with the black population. So I think that this underscores that we really need to make sure that we address the disparities in cancer care. Cancer survivorship is very important. One thing that patients complain about is insomnia. Abstract 12005 showed that yoga, cognitive behavioral therapy, and survivorship health education really improved insomnia in cancer survivors. So again, when we look at taking care of patients, we really need to look at the whole spectrum. And while we have excellent drugs and drug development that is improving outcomes, we also need to make sure that disparities, financial toxicity, survivorship are addressed. And therefore, I thought that this ASCO did a great job of looking at those issues, as well as drug development. ASCO Daily News: Absolutely. Well, thank you, Dr. Denduluri, for sharing your insights with us today on these promising new developments in the breast cancer field. Dr. Neelima Denduluri: Thank you, Geraldine. ASCO Daily News: And thanks to our listeners for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us on Apple Podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. COI Disclosure:  Dr. Neelima Denduluri Consulting/Advisory Role: Daiichi Sankyo Research Funding: Amgen, Novartis, Genentech, Lilly, Pfizer, Immunomedics

Dr. Neelima Denduluri Discusses Key Abstracts on Breast Cancer from the #ASCO20 Virtual Scientific Program

[MUSIC PLAYING] 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. Wow. 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. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcasts.

[MUSIC PLAYING] 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. Wow. 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. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcasts.

Dr. Neelima Denduluri Highlights Key Poster Presentations in Breast Cancer from ASCO's Annual Meeting