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ASCO eLearning Weekly Podcasts

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Education
Science & Medicine
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Medicine
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The ASCO eLearning Podcast is a weekly educational series focused on helping learners identify knowledge gaps and stay up-to-date with the latest in new drug developments, cancer treatments and patient care approaches.The purpose of this podcast is to educate and to inform. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. It is no substitute for professional care by a doctor or other qualified medical professional and is not intended for use in the diagnosis or treatment of individual conditions. Guests who speak in this podcast express their own opinions, experience and conclusions. Neither American Society of Clinical Oncology nor any of its affiliates endorses, supports or opposes any particular treatment option or other matter discussed in this podcast. The mention of any product, service, organization, activity or therapy on the Podcast should not be construed as an ASCO endorsement.

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The ASCO eLearning Podcast is a weekly educational series focused on helping learners identify knowledge gaps and stay up-to-date with the latest in new drug developments, cancer treatments and patient care approaches.The purpose of this podcast is to educate and to inform. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. It is no substitute for professional care by a doctor or other qualified medical professional and is not intended for use in the diagnosis or treatment of individual conditions. Guests who speak in this podcast express their own opinions, experience and conclusions. Neither American Society of Clinical Oncology nor any of its affiliates endorses, supports or opposes any particular treatment option or other matter discussed in this podcast. The mention of any product, service, organization, activity or therapy on the Podcast should not be construed as an ASCO endorsement.

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iTunes Ratings

18 Ratings
Average Ratings
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0
1
1
Cover image of ASCO eLearning Weekly Podcasts

ASCO eLearning Weekly Podcasts

Updated 11 days ago

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The ASCO eLearning Podcast is a weekly educational series focused on helping learners identify knowledge gaps and stay up-to-date with the latest in new drug developments, cancer treatments and patient care approaches.The purpose of this podcast is to educate and to inform. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. It is no substitute for professional care by a doctor or other qualified medical professional and is not intended for use in the diagnosis or treatment of individual conditions. Guests who speak in this podcast express their own opinions, experience and conclusions. Neither American Society of Clinical Oncology nor any of its affiliates endorses, supports or opposes any particular treatment option or other matter discussed in this podcast. The mention of any product, service, organization, activity or therapy on the Podcast should not be construed as an ASCO endorsement.

Rank #1: ASCO Guidelines: Use of Biomarkers to Guide Decisions on Adjuvant Therapy for Early-Stage Invasive Breast Cancer Guideline Update

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An interview with Dr. Fabrice Andre from Institute Gustave Roussy, Paris Sud University, in Paris, France on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." This update provides updated recommendations on chemoendocrine therapy for patients who present with a hormone receptor positive, HER2 not overexpressed, axillary node negative early breast cancer.

TRANSCRIPT

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. Hello, and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Fabrice André from the Institute Gustave Roussy in Paris, France, lead author on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early Stage Invasive Breast Cancer. ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." Thank you for being here today, Dr. André. Thank you. So based on the title of this guideline, we know that this update was prompted by the results of the TAILORx trial. So can you tell us more about that trial and what its results were? Yes. So the TAILORx trial was a trial that randomized two treatment modalities, endocrine therapy versus chemotherapy endocrine therapy in patients who presented what we call an intermediate recurrence cohort. So before moving to the results, maybe we can discuss a little bit the background. What we knew from the past is the fact that patients who present a recurrence score below 11 should be treated with endocrine therapy alone, because they have the good outcomes. And patients who present recurrence score that is high, 31 but also can be more on 25, should receive chemotherapy. And we are talking about patients with hormone-receptor receptor positive, HER2-negative early breast cancer without lymph node involvement. And this is extremely important. So to summarize, it's a clinical trial that includes patients with hormone-receptor positive HER2-negative lymph node negative in early breast cancer, who present with recurrence score between 11 and 25. And the question is whether we can avoid adjuvant chemotherapy in these patients who present this intermediate score. So this is the general design and the question. In terms of research, what we have learned. We have learned that for patients above 50 years old, there is no difference between endocrine therapy and chemotherapy followed by endocrine therapy. So it means that this patient or these patients, we would consider endocrine therapy alone. Then, for patients below 50 years old, there was some difference. And I think we go further into the detail. There was some difference favoring the use of chemotherapy in the group of patients who presented with recurrence score from 16 to 25. And so what changes were made to the recommendations in this update of the guideline? So first, what were [INAUDIBLE] the previous guidelines. The previous guidelines were telling the clinician which genetic tests they could use in patients with hormone-receptor positive, HER2-negative early breast cancer. Now, the big change is that we are making guideline to explain how to use the test. And what is new is that we have made three important decisions. So first, for the patient is at the age above 50, now it is recommended clinician may recommend endocrine therapy alone for women older than 50 who present a recurrence score below 26. Before, the recommendation to use endocrine therapy alone was for patient's who present with low recurrence score. So it means now we have broadened-- we have increased the number of patients who could receive endocrine therapy alone and not receive chemotherapy. Then, for patients who present a recurrence score between 16 to 25 and who are below 50 years old, the clinician may offer chemotherapy followed by endocrine therapy, meaning that we are moving from [INAUDIBLE]. This intermediate score between 11 to 25 was what we call a [INAUDIBLE]. There was no recommendation on how to use the recurrence score. So right now, the update from the ASCO guideline is to provide recommendation on which treatment to administer in case a patient presents with intermediate recurrence score, and there are two different situations above 50 years old and below 50 years old. So why are these changes so important and how will they affect practice? So they will affect practice because for many reasons, I will say. In the US, they would affect practice because they increase the number of patients who will not receive adjuvant chemotherapy, because right now, we have an answer from randomized trial that we can avoid chemotherapy in women above 50 and from 11 to 25 recurrence score. So the impact in terms of public health would be that we could have a decrease in the use of chemotherapy or at least a better precision about who should receive adjuvant chemotherapy. Globally, this trial is going to provide an incentive and increase the level of evidence supporting the use of genetic tests. So it's important to remember that in a large number of countries, genetic tests are not reimbursed. But now, because lack of evidence, and here we have a randomized trial showing a level 1 evidence supporting the use of genetic tests. So we have two direct impacts of this trial. The first, inside US, where [INAUDIBLE] colleagues already use genetic tests, it provides better precision on who will receive adjuvant chemotherapy. And it's going to broaden the number of patients who will not receive. And globally, it's prospective randomized trial that we hope is going to incite payers to reimburse the genetic test in patients with early breast cancer. And so what does this all mean for patients with early stage invasive breast cancer? And what should they talk to their doctors about? So for patients with early breast cancer, so what are the messages for the patient? I think for the patient, the key message is that we are moving to precision medicine. We need a medicine that is extremely precise in terms of who should receive which treatments. And now, thanks to this trial, we are going to decrease the number of patients who receive chemotherapy, but also for the ones who will receive adjuvant chemotherapy, the value of the treatment, we need what the treatment provides to the patient is going to be very, very high. So what is important for patients is to understand that because of this trial, when we give them chemotherapy, we will know that the value of this treatment and the expected benefit is going to be higher than what we used to do in the past. So it's really fast forward and more precise medicine that consists in using molecular tests in order to provide or administer treatment with very high value. Great. Thank you Dr. André for your overview of this guideline update. This has been very informative. It's really good to hear that the expert panel has incorporated the latest research into the guideline and has carefully considered the implications for the patients. So thank you for coming on the podcast to discuss the "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx" Thank you. What people don't realize is we did hard work that ASCO doing with all these guidelines, and people are very committed, and they are [INAUDIBLE]. I mean, it's very reassuring for ASCO member to know that there are highly professional people who provide guidelines and it is also reassuring for the patients, for everyone. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

Aug 07 2019
9 mins
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Rank #2: ASCO University Weekly Podcast Series

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Welcome to the ASCO University Weekly Podcast! Dr. Alexander Drilon from Memorial Sloan Kettering Cancer Center provides a brief overview of what you can expect from the series. Be sure to subscribe for automatic updates on new episodes and visit university.asco.org for more from our comprehensive eLearning catalog.

Apr 19 2017
1 min
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Rank #3: Recently Approved Drugs: Durvalumab for patients with stage III Non-Small Cell Lung Cancers (NSCLC)

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Rami Manochakian, M.D., a thoracic clinical oncologist at the Mayo Clinic in Florida, presents information on the recently approved drug in oncology, durvalumab for patients with stage III Non-Small Cell Lung Cancers (NSCLC) after the completion of radiation therapy.

Jun 27 2018
11 mins
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Rank #4: Special Episode: Immunotherapies

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Michael A. Postow, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses a variety of immunotherapy treatments and how they increase an immune response against tumors.

Aug 15 2018
9 mins
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Rank #5: Annual Meeting 2019 - Contrasting Cases: Molecular Profiling in Breast Cancer

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Komal Jhaveri, MD, FACP, is a breast medical oncologist with dual appointments in the breast medicine and early drug development services at Memorial Sloan Kettering Center in New York. In this special Annual Meeting 2019 episode, Dr. Jhaveri discusses two patient cases that relate to adjuvant treatment for breast cancer.

Click here to visit ASCO's Annual Meeting website to learn more about the education session. Come back after the meeting for more videos, links and information from relevant sessions.

May 22 2019
12 mins
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Rank #6: Self-Evaluation: Breast

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Rachel Freedman, MD, MPH- Assistant Professor, Medicine, Harvard Medical School, Dana-Farber Cancer Institute, presents a self-assessment question from an ASCO University course focusing on the treatment breast cancer. 

Jul 03 2018
4 mins
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Rank #7: ASCO Guidelines: Role of Treatment Deintensification in the Management of p16+ Oropharyngeal Cancer PCO

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An interview with Dr. David Adelstein of the Cleveland Clinic on the ASCO PCO which provides statements on the role of treatment deintensification in the management of p16+ oropharyngeal cancer. Read the full PCO at www.asco.org/head-neck-cancer-guidelines

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.

Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. David Adelstein from the Cleveland Clinic Taussig Cancer Institute. Lead author on "Role of Treatment Deintensification in the Management of p16 Positive Oropharyngeal Cancer: ASCO Provisional Clinical Opinion." 

Thank you for being here today, Dr. Adelstein.

Thank you, Shannon. Before we get started, I'd like to first note the contributions of my panel co-chair, Drew Ridge, and those of all of the other panel members. And I'd like to extend a special thank you to ASCO for their support in allowing us to put this together and specifically Nofisat Ismaila who did a tremendous amount of work in allowing us to complete this provisional clinical opinion.

First, can you give us an overview of the clinical issue for this PCO? Sure. So this really came out of the implications of human papillomavirus mediated oropharynx cancer. I think as most of the listeners know, over the last several decades we've recognized the fact that oropharynx cancer has a second ideology, that not all of it is caused by tobacco use, but that the human papillomavirus is now the major ideologic factor in North American and northern Europe. The importance of this is that the human papillomavirus-induced oropharynx cancer is a different disease. It has a number of different characteristics from the kinds of head and neck cancer we've seen in the past. It's a disease that tends to occur in younger patients, patients who are otherwise generally more healthy. It is unassociated with smoking, although it can occur in smokers. But it's much more frequent in nonsmokers.

And I think most importantly, it's a disease that has a dramatically better prognosis than the tobacco related disease. Now over the last several decades, our ability to treat advanced head and neck cancer has improved significantly, because we've begun to incorporate non-operative treatments-- chemotherapy and radiation-- and have been more aggressive in our utilization of chemotherapy and radiation with significantly greater success than we had in the past. The problem with this kind of treatment is that it is quite rigorous. And there's a good deal of acute and, more importantly, late toxicity that patients experience from these kinds of approaches. Now as we became more familiar with the importance of HPV associated oropharynx cancer, we realized that there are subgroups of these patients who have cure rates that are in excess of 90%. And the question arose whether the kinds of rigorous chemotherapy and radiation therapy treatments that we were utilizing were really necessary. Was it necessary to cause this much acute and late toxicity in patients who in vast majority of cases were going to be cured of the disease.

And it's important, because these are younger patients. And the late toxicities are going to have a major impact on their quality of life for a number of years.

What came about was the notion of treatment deintensification, the idea that perhaps it would be possible to deintensify the kinds of treatments we were giving in select patients. It's a very compelling hypothesis for medical oncologists and radiation oncologists. But there are a number of problems as we try to test this hypothesis. The first problem is how do we identify the good risk patients? There are patients with HPV-positive disease who do not do so well-- the heavy smokers and patients with very advanced tumors. And we need to be careful if we're going to be talking about giving less treatment that we don't give less treatment to the patients who have a worse prognosis. We pick the best prognosis patients.

There have been a number of what we call risk stratification schemes that have been developed looking at trying to identify the very good prognosis patients-- those patients who are HPV positive who don't smoke and who have relatively limited disease extent. There's not universal agreement on how best to define these patients. All we know is that they do exist, that you can look at patients with these characteristics and see very good outcomes. One of the issues that has come up is how do we utilize the American Joint Committee staging system-- AJCC the 8th edition. One of the things that AJCC 8 did which is new is that it defined a separate staging system for patients with HPV-positive oropharynx cancer, a system which is entirely different than the staging system that we've used for head and neck cancers for many years. This was based on the recognition that the prognosis of patients with HPV-positive disease is so good so that many patients who we would previously have considered to have stage 4 disease are now classified as having stage 1 tumors, because their prognosis is so good. And that can be confusing, because the typical thought process for an oncologist is that a patient with stage 1 disease should be treated with single modality therapy.

The reason that the HPV-positive patients have such a good prognosis, however, is that many of them have been treated with combined modality therapies. And to make the assumption that because now they're classified as stage 1 is incorrect. It is they shouldn't be treated with less intensive treatments and can be confusing. AJCC 8th edition is a prognostic robust staging system, but it really doesn't help us in defining treatment.

First problem is how best to define patients who are appropriate for deintensification. Second problem is, what do you do to deintensify? What constitutes meaningful deintensification?

Well, over the last 10 or 20 years there have been some significant advances in our standard treatments for all head and neck cancers that weren't developed the idea of deintensification. We now have tremendous experience using transoral surgical techniques, which are generally minimally morbid, much less morbid than the former open techniques that previously were used, which allows consideration of surgery for many of these patients where we wouldn't have considered it before.

Similarly, intensity modulated radiation therapy has been widely adopted, and d clearly an approach using radiation, which is far less difficult, far less toxic than the former 2D or 3D radiation planning techniques that used to be used.

But if we talk about intensification, what kinds of things can we do to deintensify our treatments? Well, one thought is to reduce the radiation dose. Then the question is, how much reduction is reasonable? And how much reduction is going to actually impact on this toxicity? And are our toxicity measuring tools adequate to even detect the difference in reduction of a radiation dose? Many of our toxicity tools are very crude. Perhaps we should be using some of the patient-reported outcome quality of life instruments that are available.

Other thoughts are, perhaps one can reduce the size of the radiation therapy field. Can we reduce the dose of the chemotherapy? Can we eliminate chemotherapy? Can we even use less intensive chemotherapy? Generally, the other treatments for this disease have employed high doses of cisplatin, which is a toxic agent.

And then there the question has been asked as to whether we can reincorporate minimally morbid transoral surgical techniques in an effort to better pathologically stage patients and define more appropriate adjuvant treatment. Perhaps not all patients need adjuvant radiation or chemotherapy and radiation.

All of these approaches are interesting. They're exciting. They're being tested. But all of the experiences is preliminary.

And that really brings us to the third and the biggest problem in any deintensification approach. And that's the need to be certain that if we deintensify our therapy, we're not going to compromise outcomes. It would not be acceptable to give less treatment or less intensive treatment if our survival were compromised. And we have to be certain that we don't do this.

So what has evolved over the past decade is a whole number of treatment approaches that have some very enthusiastic early results. But these are generally single arm phase 2 reports where there is no comparison to conventional treatment. And they become difficult to interpret, because the results in general are very good. I think what really raised a red flag for us and that really caused us to take notice was the results of the RTOG 1016 trial that we reported last year. And at the same time, the European de-escalate trial, both of which had a similar design. These were studies that were designed in an effort to see if treatment deintensification would be possible by randomly comparing the standard treatment radiation and cisplatin with what was felt to be a less intensive approach-- radiation and concurrent cetuximab. And cetuximab is an accepted agent in the United States for treating head and neck cancer.

The assumption here is that the survival would be equivalent when these two arms were compared, but that the toxicity would be improved by giving the less intensive systemic agent-- the cetuximab. The surprise when the study was analyzed was that that assumption was incorrect, that the radiation and cetuximab arm-- the deintensified arm-- actually proved inferior in terms of survival. And this was in both trials-- both the RTOG trial and the trial from Europe. And that was a big note of caution, because it was somewhat unexpected. I think we learned from that kind of a study, from a good randomized-- a large randomized trial-- that even though the outcomes may appear to be good, we need to be very careful about deintensifying our treatment until we're sure that the survival is equivalent.

So although it's tempting for the clinician to see these very exciting reports about administering less treatment with the idea of producing less toxicity, the guideline advisory committee for ASCO really thought it was important that we get the message out that this kind of approach is not a treatment standard. This remains an investigational approach, and that the treatment standards for this disease really haven't changed.

So what are the provisional clinical opinions that were made by the expert panel?

They made several statements. The first was to acknowledge that the idea of treatment deintensification is a very compelling hypothesis, and it does require careful and appropriate testing. The second was that even though we are now better at identifying good prognosis patients, and we've seen some very promising early results, and even though we're now reclassifying patients with previously advanced stage HPV-positive disease as stage 1 or stage 2 tumors, the treatment recommendations for this disease have not changed. And they're based on the results achieved using AJCC 6 and 7.

Standard of non-operated management to patients who are eligible to receive cisplatin remains high concurrent radiation and high dose cisplatin given every three weeks. If patients undergoing a surgical resection, then adjuvant chemotherapy and radiation with radiation and high dose cisplatin every three weeks is recommended in those patients with high risk factors of positive surgical margins or external tumor extension.

And most importantly, deintensification, though it's a compelling hypothesis, is something that should only be undertaken on a clinical trial.

Why is this guidance so important? And how will it affect practice? Well, I think the important thing about this guideline is that it shouldn't affect practice. The practice shouldn't change. The standards of care are not altered. And that for the clinician, this remains something that is exciting, something that should encourage enrollment on a clinical trial, but that we haven't changed treatment standards.

And finally, how will this guidance affect patients?

So from a patient's point of view, I think there is continued reason for optimism. A patient with the diagnosis of an HPV-positive oropharynx cancer is a patient with a very good prognosis. Patients are increasingly sophisticated. They read about the potential for treatment deintensification, and recognize that this is not something which is an accepted standard. But it should encourage their participation in clinical trials if [INAUDIBLE] is offered.

I think ultimately it's a remarkable thing when oncologists can consider the possibility of reducing treatment intensity because the treatment results have been so good.

Great. Thank you for your overview of this PCO. And thank you for your time today, Dr. Adelstein.

And thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full PCO, go to www.asco.org/head-neck-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Jul 31 2019
14 mins
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Rank #8: ASCO Guidelines: Pancreatic Cancer

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Dr. Edward Balaban, medical director of the Cancer Care Partnership at Penn State Health, presents the ASCO Clinical Practice Guideline on locally advanced, unresectable pancreatic cancer, originally published in the Journal of Clinical Oncology in August 2016.

May 31 2017
8 mins
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Rank #9: ASCO Guidelines: Palliative Care

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Betty Ferrell, PhD, MA, FAAN, FPCN, director of the Division of Nursing Research and Education and professor at City of Hope National Medical Center, presents the ASCO Guideline on Integration of Palliative Care into Standard Oncology Care, originally published in the Journal of Clinical Oncology in January 2017.

May 10 2017
5 mins
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Rank #10: ASCO Guidelines: Secondary Prevention of Cervical Cancer

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Dr. Philip Castle, Professor in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine, presents the ASCO Guideline on Secondary Prevention of Cervical Cancer, originally published in the Journal of Clinic Oncology in October 2016.

Jul 19 2017
5 mins
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Rank #11: Recently Approved Drugs: Nivolumab for patients with metastatic small cell lung cancer

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Victoria Lai is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center with a clinical and research focus on small cell lung cancer and other pulmonary neuroendocrine tumors.  She conducts clinical trials that aim to elucidate the underlying biology of small cell lung cancer in order to develop new biomarkers and treatments options to improve patient outcomes.

TRANSCRIPT

[MUSIC PLAYING]

Welcome to the recent approvals episode of the ASCO University weekly podcast. My name is Victoria Lai. I am an assistant attending physician in a thoracic oncology service at Memorial Sloan Kettering Cancer Center. Today, we will discuss the approval of nivolumab for the treatment of patients with metastatic small cell lung cancer in the third-line setting. As a background to today's discussion, we know that FDA approved therapies for small cell lung cancer are extremely limited and remain a large, unmet need. Immune checkpoint inhibitors, including nivolumab, are active therapies in several different tumor types. Nivolumab is a monoclonal antibody against PD-1 and has previously been shown to be effective in non-small cell lung cancer.

More recently, the role of immune checkpoint inhibitors in the treatment of small cell lung cancer has been explored in an effort to develop more effective treatment options for these patients. On August 16 2018, nivolumab was granted an accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression after prior platinum-based chemotherapy and at least one other line of treatment regardless of PD-L1 expression of the tumor.

This approval of nivolumab in the third-line setting in small cell lung cancer was based on results from the CheckMate 032 study that was initially published in The Lancet in 2016 and has since reported updated results. CheckMate 032 was a multi-center open-label trial in patients with metastatic solid tumors. The study included a subgroup of 109 patients with metastatic small cell lung cancer who experienced disease progression after platinum-based therapy and at least one other line of therapy regardless of tumor PD-L1 status. All patients received nivolumab 3 milligrams per kilogram by intravenous infusion over 60 minutes every two weeks.

The primary endpoint of this study was the objective response rate. The overall response rate was 12% with a 95% confidence interval between 6.5 to 19.5% with responses seen in 13 out of 109 patients. Responses were durable for six months or longer in 77% of patients, 12 months or longer in 62% of patients, and 18 months or longer in 39% of patients. PD-L1 tumor status did not appear to be predictive of response.

Of all the patients who received at least one dose of nivolumab, the most common side effects were fatigue, decreased appetite, musculoskeletal pain, dyspnea, nausea, diarrhea, constipation, and cough. Serious adverse reactions occurred in 45% of patients and included pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration. The recommended dosing schedule of nivolumab for this approved indication is 240 milligrams every two weeks over 30 minutes.

The approval of nivolumab as subsequent line therapy marks a significant advancement in the treatment of patients with metastatic small cell lung cancer. Prior to this, topotecan was the only other agent approved by the FDA for treatment in this setting, which did not yield durable responses. Although the response to nivolumab was modest, the majority of patients responded to treatment were able to achieve durable responses of greater than 12 months with over 1/3 of patients achieving a durable response of greater than 18 months. Further more, responses to nivolumab were seen regardless of the patient's prior response to chemotherapy.

Given that topotecan yields a response rate in the single digits as subsequent line therapy for chemo-resistant disease, nivolumab adds an especially valuable treatment option for these patients whose disease did not previously respond to chemotherapy. Nivolumab adds an especially valuable treatment option for these patients whose disease did not previously respond to chemotherapy. Responses to nivolumab were also seen in patients who had exceeded three prior lines of therapy indicating that nivolumab can still be effective in heavily pre-treated patients.

With 45% of patients in this study having developed a serious adverse reaction, patients undergoing treatment with nivolumab should be monitored closely. Finally, this study did not show any correlation or responses to nivolumab with PD-L1 expression, suggesting that the role of PD-L1 as a predictive biomarker in small cell lung cancer remains unclear. Thank you for listening to this week's episode of the ASCO University weekly podcast. For more information on immunotherapy and the treatment of small cell lung cancer, please visit the comprehensive eLearning center at university.asco.org.

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.

Sep 05 2018
5 mins
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Rank #12: Recent Approvals: Duvelisib for Adult Patients with Relapsed or Refractory CLL or SLL

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Dr. Ian Flinn, Medical Oncologist specializing in hematologic malignancies at Tennessee Oncology, discusses the recent FDA approval of duvelisib for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

(Intro Music Playing) As a background to today's discussion, the PI3K are a family of lipid kinases that sit at the crossroads of numerous signaling events that drive many malignancies, including certain lymphomas, and chronic lymphocytic leukemia. There are four isoforms of the PI3K-- alpha, beta, delta, and gamma. Isoform specific inhibitors are attractive because they may lead to efficacy without the toxicity of pan inhibitors.

Idelalisib, which is a delta isoform inhibitor, was the first PI3K inhibitor be approved for lymphoma in CLL. The delta isoform is a particular interest in B cell malignancies because its expression is normally restricted to cells of a hematopoietic origin. In data from gene knockout models, show that it has a key role in B cell signaling, development, and survival. Selective targeting of the delta isoform should not alter insulin signaling, which is mediated by the ubiquitously expressed alpha isoform. However, narrow targeting could lead to mechanisms of resistance to upregulation of other isoforms. This has been demonstrated in mantle cell lymphoma where the alpha isoform is expressed in relapse patients.

Duvelisib is a dual inhibitor of both the delta and gamma isoforms of the PI3K. Inhibiting the gamma isoform may be important because of its inhibitory effect, not only in the malignant cell, but also in the micro-environment, which provides important survival signals to malignant cells. Both idelalisib and copanlisib, an inhibitor of the delta and alpha isoforms, are currently FDA approved for third line follicular cell lymphoma. And idelalisib is approved in combination with rituximab in relapse CLL.

On September 24, 2018, the Food and Drug Administration granted approval for duvelisib for patients with relapsed refractory chronic lyphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma after at least two prior therapies. The approval of duvelisib in CLL was based on the DUO trial, a large international randomized phase III trial comparing duvelisib, at 25 milligrams orally, twice daily, to ofatumumab, given according to the package label. The results of the duo trial have been published in Blood. In a subset analysis of 196 patients receiving at least two prior therapies, the median progression pre-survival was 16.4 months in the duvelisib arm, and 9.1 months in the ofatumumab arm, with a hazard ratio of 0.40. The overall response rate of 78% with duvelisib was twice the 39% seen with ofatumumab.

The follicular lymphoma indication is based on the Dynamo trial, a single arm multi-center trial of duvelisib, which enrolled 83 patients with follicular lymphoma who are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The overall response rate, determined by an independent response committee, was 42%. Of the 35 responding patients, 15, or 43%, maintained responses for at least six months. And 6, or 17%, maintained responses for at least 12 months. The most common adverse reactions with an instance of greater than or equal to 20% were diarrhea, or colitis, neutropenium, rash, fatigue, pyrexia, cough, nausea, upper respiratory tract infection, pneumonia, muscle skeletal pain, and anemia.

Over the last decade, we've seen substantial advances in the treatment of low grade lymphoma and CLL, especially in the front-line setting. Unfortunately for patients with relapse and refractory disease, new agents are needed. The approval of duvelisib is an important addition to our armamentarium for these patients. And we'll have an immediate impact.

However, to have its greatest effect, strategies will need to be devised to move this drug earlier in the natural history of these diseases. Such approaches might include alternative dosing and scheduling, as well as combination regiments. Duvelisib is a novel PI3K inhibitor and is differentiated from other PI3K inhibitors, because it targets both the delta and gamma isoforms. Consequently, it is being studied in a broader array of diseases, including T cell malignancies, where promising activity has been seen.

(Outro Music Playing) Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on drug approvals visit the comprehensive e-learning center at university.asco.org.

Jan 30 2019
4 mins
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Rank #13: Immunotherapy and Changes in Standard Practice in Local Regionally Advanced Non-Small Cell Lung Cancer

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May 15 2019
7 mins
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Rank #14: ASCO Guidelines: Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers

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Saro H. Armenian, D.O., MPH, pediatric hematologist/oncologist at City of Hope, presents the ASCO Guideline on prevention and monitoring of cardiac dysfunction in survivors of adult cancers, originally published in the Journal of Clinical Oncology in March 2017.

Jun 28 2017
5 mins
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Rank #15: ASCO Guideline: Metastatic Pancreatic Cancer

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TRANSCRIPT

[MUSIC PLAYING]

Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I'm the clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and editorial board member for ASCO University.

Today we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel.

[MUSIC PLAYING]

Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Davendra Sohal from Cleveland Clinic, lead author on Metastatic Pancreatic Cancer American Society of Clinical Oncology Clinical Practice Guideline update. Thank you for being here today, Dr. Sohal.

Thanks for having me. It's a pleasure.

So this update is focused on revising the recommendations on second line treatment for metastatic pancreatic cancer. Can you tell us about the studies that informed this update?

Certainly. The first study is a paper published in Science on PD-1 inhibition and solid tumors. This study included 86 patients with mismatch repair deficient tumors, also known as microsatellite instability high tumors.

In this study, 53% of the patients had an objective response with a disease control rate of 71% across multiple histologies. The study also included eight patients with pancreatic cancer, two of whom had complete responses with a disease control rate of 75%. This is the study that informed our recommendation for checkpoint inhibitor therapy in the second line setting.

The second study is the PANCREOX trial published in JCO, which randomized patients to 5-fluorouracil or FOLFOX. With 108 patients, the primary outcome of overall survival was 9.9 months in the control 5-fluorouracil arm, and surprisingly, only 6.1 months in the FOLFOX arm. This study informed our recommendation for chemotherapy regimens in the second line setting.

And what are the new and updated recommendations for second line treatment?

For second line treatment of metastatic pancreatic cancer, our first recommendation now is to consider testing for mismatch repair deficiency or microsatellite instability in patients who are candidates for checkpoint inhibitors therapy. Any standard form of testing is acceptable, whether IHC or PCR or next-gen sequencing.

Patients who have mismatch repair deficient or microsatellite instability high tumors should be treated with pembrolizumab given the excellent responses noted in the study we just discussed. For patients who do not meet these criteria for checkpoint inhibitor therapy, second line therapy with gemcitabine plus nab-paclitaxel can be offered to those who received FOLFIRINOX in the first line and meet other criteria for aggressive chemotherapy as detailed in the guideline.

Now, for patients who receive gemcitabine plus nab-paclitaxel in the first line, fluorouracil plus nanoliposomal irinotecan is the preferred second line therapy. Where nanoliposomal irinotecan is not accessible, fluorouracil plus regular irinotecan is an acceptable alternative.

As I mentioned the combination, of 5-fluorouracil plus oxaliplatin can be considered as an option in this setting, but we have noted a qualifying statement about the PANCREOX study whose results are inconsistent with the CONCORD-3 study using the same agents as the off regimen. Given these conflicting results from different studies of 5-fluorouracil plus oxaliplatin, the recommendation for its use in the second line setting has been softened.

Can you also give us an overview of the recommendations from the original 2016 version that the expert panel decided were still valid?

Sure. In 2016, the expert panel made recommendations which span from initial assessment through to follow up and surveillance. For every patient with metastatic pancreatic cancer, a multi-phase CT scan should be performed and baseline performance datas and comorbidities should be evaluated. Goals of care should be discussed with a multidisciplinary team, and all patients should be offered information about clinical trials.

Outside of a clinical trial, standard first line treatment options include FOLFIRINOX, gemcitabine plus nab-paclitaxel, or gemcitabine alone. And the full guideline provides details on which treatment is appropriate for which patients. The panel also recommended that every patient should be offered palliative care early in their treatment. These recommendations were endorsed in the update and are reprinted in totality in the bottom line box on the second page of the article.

And finally, what are some important things to note about communicating with patients with pancreatic cancer, especially in the metastatic setting?

Excellent point. It is important to communicate that participation in clinical studies is strongly encouraged. These studies could include new treatments, or supportive care measures, or collection of blood and tumor samples for further research, et cetera. While chemotherapy forms the backbone of treatment, it is only one component, and that is an important point to make.

The use of supportive care or palliative care is strongly encouraged for all patients with metastatic pancreatic cancer in order to maximize not just the quantity, but also the quality of life.

Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. Sohal.

Sure. Thank you very much. I'd like to thank our panel for diligent data review and dedicated discussions and the ASCO staff for all their support in producing the update. Thank you.

And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

[MUSIC PLAYING]

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.

Oct 17 2018
7 mins
Play

Rank #16: Self-Evaluation: Non-Small Cell Lung Cancer (NSCLC) Screening

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If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

Welcome to the Self-Evaluation episode of the ASCO University weekly podcast. My name is Apar Kishor Ganti, and I'm the Associate Director for Clinical Research and the co-leader of the Thoracic Oncology Service at the University of Nebraska Medical Center, Fred and Pamela Buffett Cancer Center.

Today, we feature a self-evaluation question on locally advanced non-small cell lung cancer. I will begin by reading the question stem. A 58-year-old man with a 50-pack year history of smoking presents to your clinic with worsening cough and shortness of breath. His comorbidities include irritable bowel syndrome and coronary artery disease.

A CT scan of the chest, abdomen, and pelvis reveal a two-centimeter right lower lobe mass with no evidence of lymphadenopathy in the chest. A positron emission tomography scan confirms a hypermetabolic right lower lobe mass and mildly avid mediastinal nodes. An MRI of the brain was performed and was negative.

A biopsy of the right lower lobe mass was positive for squamous cell carcinoma of the lung. The patient was taken for a mediastinal lymph node evaluation by a thoracic surgeon. Additional biopsies of multiple lymph nodes were taken. Pulmonary function tests revealed that a right lower lobectomy would be feasible if warranted.

Which of the following would lead you to recommend definitive chemoradiation rather than surgery as the most appropriate treatment for this patient? The answer choices are, A, metastatic squamous cell carcinoma identified in a left hilar lymph node, B, metastatic squamous cell carcinoma identified in a right hilar lymph node, C, the absence of squamous cell carcinoma in a left paratracheal lymph node, and D, the absence of squamous cell carcinoma in a right hilar lymph node?

[MUSIC PLAYING]

The correct answer to this question is A, metastatic squamous cell carcinoma identified in a left hilar lymph node. In the eighth edition of the AJCC TNM classification system, this tumor would be classified as T1B.

The presence of cancer in a contralateral hilar lymph node represents N3 disease and thus, stage 3B. Surgery is not recommended in this setting, and definitive chemoradiation is considered standard of care.

What about the other choices? Involvement of an ipsilateral hilar node would only represent N1 and stage 2B disease, for which a right lower lobectomy and mediastinal lymph node dissection are appropriate.

The absence of involvement of the left paratracheal node would confirm the absence of N3 disease, while the absence of involvement of the right hilar node would confirm the absence of N1 disease. In both these scenarios, the patient would be considered resectable if other lymph node stations are not involved.

Thank you for listening to this week's episode of the ASCO University weekly podcast. For more information on lung cancers, including important release for self-evaluation, visit the comprehensive E-Learning Center at university.asco.org. Thank you.

[MUSIC PLAYING]

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.

Nov 07 2018
4 mins
Play

Rank #17: ASCO Guidelines: Treatment of Multiple Myeloma

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TRANSCRIPT

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. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and I'm interviewing Dr. Joe Mikhael from the City of Hope Cancer Center and International Myeloma Foundation, lead author on "Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline." Thank you for being here today, Dr. Mikhael. It's a pleasure to be with you. So first, can you give us some context as to why this guideline was developed? Well, we had a lot of ideas when we put together this guideline, but most importantly, multiple myeloma continues to be a rare disease in the cancer world. It really only accounts for about 1% to 2% of cancers. So for the practicing oncologist, they spend perhaps 3-ish percent of their time doing multiple myeloma. And when you add to that there has been really a revolution in myeloma with new drugs approved, new treatments, new approaches, it really leaves the general oncologist with a complexity of how to treat this disease. And so we wanted to create a very practical guideline that would give very precise advice to walk through how one would care for a multiple myeloma patient, right from their diagnosis to indeed relapse disease. We felt this approach was so important now, more than ever, because of the fact that myeloma has really changed so much, and now, thankfully, we're seeing our patients live so much longer that the treatment options can become a little bit more complicated over time. Furthermore, we partnered with Cancer Care Ontario, because this was really felt to be not just an American phenomenon, but really a full North American phenomenon of how we could work together to really give practical advice as to how to treat this disease. So what are the key recommendations of this guideline? In this guideline, we focused really on the treatment of the disease itself. There have been other guidelines that have focused on supportive care and bone disease and multiple myeloma, but we really focused on the treatment of patients really from induction therapy through to relapse. So we spend time helping guide the decision around whether or not a patient is transplant eligible or ineligible, because that's really the first dividing marker in myeloma, because we know that transplant still has a role in myeloma, and eligible patients should have a transplant, or at least have access to a transplant. And historically, this was really done on the basis of age. But the guidelines helps the clinician see that it's really not just an age phenomena. It's really a decision based on comorbidities and really what's best for the patient. So we spend time helping making that decision, and then provide very practical advice as to how to treat a patient who's going to transplant versus a patient who's not going to transplant. We also, then, after the transplant, or in lieu of a transplant, we discuss the importance of continuous therapy, or sometimes called, maintenance therapy in myeloma. Again, we've seen maintenance therapy, now, have an impact on both progression free and overall survival. And so we felt it was really important to be very practical in giving advice as to what maintenance therapy agents to use and how to use them. And then lastly, the guideline provides a lot of practical advice as to a patient who has relapsed with multiple myeloma. We have so many choices now with three major classes of drugs of proteasome inhibitors, immuno-modulatory drugs, and now newer monoclonal antibodies, it can be difficult sometimes to know which combination to use. We know that triplet combinations tend to be preferred. So we walk through a number of those triplets and provide advice as how to explicitly use them. We do emphasize the importance of supportive care and of risk factor analysis throughout the guideline, so that we can understand the difference between high risk and low risk myeloma, so that we can understand how important a patient's comorbidities, especially in a disease that primarily affects older patients, can be managed. And so we try to do so in a comprehensive way, but one that really distills down to the critical pieces to allow the practicing clinician some real advice. So why is this guideline so important, and how will it change practice? There are several kinds of guidelines for multiple myeloma, but I really think this is a critical guideline because it is so clinical and practical in its essence. It's really designed to not just give the utopian view or the clinical trial view of a disease, but practically in the trenches, how do we use the drugs that we know are going to benefit our patients. Myeloma is one of the few cancers where we have seen a doubling, if not a tripling of survival in the last decade, because of so many of these new agents. And so making sure that our patients are treated optimally really is important. And we want to be able to ensure that they receive the best therapy possible, so they can live a longer life, but also live it with a greater quality of life. And so finally, how will these guideline recommendations affect patients? Well, we really hope that this is going to help patients all across North America and the whole world, because it will give very concrete advice to the practicing clinician in how to approach the disease. And one of the things I think will directly impact patients, if you will, right away is one of the themes of these guidelines, which is that you don't treat a patient simply based on the biopsy or simply based on their age, but that it is really a complex network of comorbidities, risk factors from the disease itself, the potential side effects of certain drugs, and a patient's own very personal history. It really fits in with the ASCO modality that we have of ensuring that we bring personalized medicine to our patients. And so this will allow the person who's reading it and who's applying it to their patient to recognize the importance of general guidelines, but also of applying it to the specific patient they care for. Because as I like to say, we don't treat multiple myeloma, we treat people. And so hopefully, this will allow the clinician to have that precision to care for their patient in the best way possible. Great. Thank you for that overview of this guideline, and thank you for your time today Dr. Mikhael. It's been a real pleasure. Thank you very much. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/hematologic-malignancies-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

Apr 03 2019
7 mins
Play

Rank #18: ASCO Guideline: Palliative Care in the Global Setting

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Shadia Jalal, MD, Assistant Professor of Clinical Medicine in the Department of Medicine, Division of Hematology/Oncology at Indiana University School of Medicine discusses updated guideline for palliative care in the global setting.

TRANSCRIPT

Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I am the clinical director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and editorial board member for ASCO University.

Today, we feature an ASCO Guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently-published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel.

[MUSIC PLAYING]

Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernan, and today, I'm interviewing Dr. Nahla Gaffer, from the Radiation S Isotope Center in Sudan, an author on palliative care in the global setting, American Society of Clinical Oncology resource-stratified practice guideline. Thank you for being here today Dr. Gaffer.

Good morning. Thank you, so much, Mrs. Shannon for this opportunity.

First, can you give us a general overview of what this guideline covers, and what it means to be a resource-stratified practice guideline?

Yes. These guidelines outline and they cover the recommended set of palliative care integration concerning personnel needed, training needed for this staff, structure, and availability of medicines at different resource levels. And by a resource-stratified guideline, we mean that it's suitable for different levels of development. Yes.

For example, if you are speaking about a community level, you are speaking of primary care centers, or if we are speaking about in a different setting, like a regional hospital and also, the highest level might be the oncology center. And at every level, there should be a better structure and better training and availability of palliative care. But at all of these levels, we should have palliative care.

What are the key recommendations of this guideline?

Yes. The key recommendations, as I mentioned, is that we should have a coordinated system, where the patient's palliative care needs are identified and met at every level and from the moment of diagnosis.

So we are speaking about, at the basic level, we should have at least a volunteer or community worker or better even, a nurse trained in palliative care. And these people have got the job to facilitate identification of patients who need palliative care at the community level.

Another level is the limited level, and here, we should have at least one doctor and a nurse trained in basic palliative care, and they work with the people working in the community. And they address minor issues, prescribing basic medicines, referring patients, and they also have the ability to support the patient and the family in [INAUDIBLE].

At another enhanced level, and we are speaking here about setting like a regional hospital, there should be a team, at least of three personnel-- doctor, nurse, pharmacist. Of course, if there is a psychologist or religious chaplain, it's OK, but at least these three personnel should be trained about palliative care, so a minimum of six weeks training. And they can provide palliative care, and they can offer as outpatient service in this regional hospital.

The best setting or the maximum setting is when we are speaking about a bigger hospital or an oncology center. And we are speaking that no oncology center or any facility for palliative care patients, like hospices, should exist without a well-developed palliative care team. And having personnel and all personnel working in that center should receive basic training in palliative care.

The main treating doctors, for example, the oncologists, should have secondary training in palliative care, so it's a higher level of training in palliative care. And we need for palliative care physicians to supervise and develop the service. At such a setting, we should have psychologists, we should have chaplains all integrated in the service.

Another recommendation is that palliative care should be given and provided at all levels ideally, at the moment of diagnosis of the patient, but especially for patients who are coming with overwhelming symptoms, whether physical, psychological, or spiritual or patients who have metastasis or patients who cannot receive active treatment for curative intent, for example, for comorbidities or age or patients with a disease with a known short life expectancy. All these patients should receive palliative care from the moment of diagnosis.

Why is this guideline so important, and how will it change practice?

Yes, it is very important because palliative care is important to be given to all patients at every setting. It is not expensive. It doesn't require special equipment. It can be given. It not only should be given, but it can also be given. It's not difficult to change.

And this guideline is very important, because sometimes people don't hear other colleagues or junior doctors. They hear high recommendations, like from the ASCO guidelines.

And finally, how will these guideline recommendations affect patients?

Yes. We hope the directors of hospitals, people or personnel at administerial levels, our fellow colleagues, they embrace these recommendations more and more. As I mentioned, sometimes it needs to come from higher up, and for that, we thank the American Society of Clinical Oncology for taking this task.

Once we are caring for our patients holistically, which includes social, spiritual, psychological dimensions, in addition to physical, it leads to a better quality of life, affecting not only the patient and the family in all dimensions but even leading to a better survival, and here, I mean both in time and quality.

Great. Thank you for your time today, Dr. Gaffer.

Thanks. Thanks a lot.

And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

[MUSIC PLAYING]

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.

Aug 29 2018
8 mins
Play

Rank #19: ASCO Guidelines: Adjuvant Endocrine Therapy for Women with Hormone Receptor Positive Breast Cancer Guideline

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TRANSCRIPT

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.

Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Jennifer Griggs from the University of Michigan, senior author on "Adjuvant Endocrine Therapy for Women with Hormone Receptor Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update." Thank you for being here, Dr. Griggs.

And thank you for the opportunity to talk about this focused update to the guidelines on extended adjuvant therapy. I would, of course, like to thank all my co-authors in the ASCO guidelines team for their contribution to this effort.

So first, can you give us a general overview of what this guideline covers and their research which informed this focus update?

Yes. First of all, the goal of the guideline was to give an update to the previous guidelines on this topic. And we specifically focused on extended adjuvant therapy. In particular, the aromatase inhibitors in women who had completed five years of adjuvant endocrine therapy. And it goes without saying, but it's worth reminding our listeners that the guideline is restricted only to post-menopausal women with hormone receptor-positive breast cancer. And, of course, our guidelines are only as good as the data upon which we rely. So for this guideline, six phase III randomized controlled trials met the pre-specified eligibility criteria for the updated systematic review and provide the evidence base for the guideline recommendations on the duration of aromatase inhibitor therapy. Each of the trials used the standard doses of the drugs that we use in practice today. So I'm not going to say the doses of each of the medications. So I'm going to go briefly over those six trials and just describe them so everybody's up to date with how the studies were designed.

So briefly, the first trial I'll describe is MA17R, which compares letrozole to placebo for five years in over 1,900 women who had already received 4.5 to six years of adjuvant therapy with an AI, proceeded in most women by treatment with tamoxifen. The second study is NSABP B-42. And this also compares letrozole to placebo in nearly 4,000 women who'd completed five years of endocrine therapy with either five years of an aromatase inhibitor or up to three years of tamoxifen followed by an aromatase inhibitor, for a total of five years.

The third study that we looked at is the DATA trial, which stands for the Different Durations of Adjuvant Anastrozole Therapy. This trial compared six years of adjuvant anastrozole with three years of adjuvant anastrozole in over 1,600 women after two to three years of adjuvant tamoxifen. The fourth trial out of the six is the IDEAL trial, the Investigation on the Duration of Extended Adjuvant Letrozole. This study randomized over 1,800 women to either 2 and 1/2 or five years of letrazole after five years of tamoxifen, an AI, or a combination in sequence of tamoxifen and an AI. So very similar study designs.

The fifth study is the ABCSG-16 trial, the Austrian Breast Cancer Study Group Trial 16, which randomized nearly 3,500 women following four to six years of adjuvant therapy with tamoxifen and AI or a sequence of tamoxifen and then an AI, to either two or five years of anastrozole as extended therapy. And finally, the study of letrozole extension, or the SOLE trial, randomized over 4,800 women with node-positive breast cancer who had completed five years of adjuvant endocrine therapy to receive either continuous letrozole for five years or five years of an intermittent schedule of letrozole given nine months on and three months off in years one to four and on continuously for a year or five.

So I know that's a lot to take in, but I do think it was important for our audience to understand the six trials that were included. These were all large studies, randomized, and patients had completed five years of adjuvant endocrine therapy. And then, were randomized either to placebo or different durations of an aromatase inhibitor or a placebo. For all of these studies, it's important to know that the primary outcome was disease-free survival. Overall survival and adverse events where secondary outcome.

Great. So given that research and those trials, what are the key recommendations for this guideline update?

Five key recommendations are included in this focused update to the previous guidelines. And they are for women with node-negative breast cancer, extended adjuvant aromatase inhibitor therapy can be offered for up to a total of five years of adjuvant therapy. Recommendations are based on considerations of recurrence risk using our usual established prognostic factors. However, since the recurrence risk is lower, the benefits are likely narrower in node-negative patients.

The guidelines panel recommends that women with low-risk, node-negative tumors should not routinely be offered extended adjuvant therapy. Now, that might sound vague. We did not make recommendations using genomic profiling results because we don't have sound data to support such views that we felt were strong enough to integrate genomic testing results. Our second recommendation is that women with node-positive breast cancer should be offered extended AI therapy for up to a total of 10 years of adjuvant endocrine therapy. And that means combined tamoxifen and aromatase endocrine therapy. That's the total that we meant to recommend.

Third recommendation is that women receiving extended adjuvant endocrine therapy should receive no more than 10 years of total treatment. The fourth recommendation is when given as prevention of secondary or contralateral breast cancer, the risk of second breast cancers based on prior therapy should inform the decision to pursue extended therapy. So what this means is specifically, a woman who has had a bilateral mastectomy will not reap the benefit of preventative therapy with endocrine therapy.

The fifth recommendation is that extended therapy carries ongoing risks and side effects, and these should be weighed against the potential absolute benefits of longer treatment in a shared decision-making process between the clinical team and the patient. Specifically, to date, none of the studies have shown improvement in overall survival with longer duration aromatase inhibitor therapy. As such, the recommendations, therefore, an extended adjuvant AI therapy are based on benefits that include prevention of distant recurrence and prevention of second breast cancers.

So why is this guideline so important and how will it change practice?

The importance of this guideline rests in the fact that it supports what many clinicians and patients are already doing in practice. The second is it recommends against durations of endocrine therapy longer than 10 years in the absence of data supporting such a practice. So it's our thought that doctors and patients and other care providers, nurse practitioners, physician assistants, primary care doctors, are already practicing what we're recommending, and it supports doing so. And the second is that for those providers and patients who aren't sure that 10 years is enough, this guideline suggests that 10 years is sufficient. We don't have any data supporting giving more than 10 years.

And the third recommendation is that this guideline really supports the need for shared decision-making, given the absence of data supporting an improvement in overall survival.

So finally, since you did mention shared decision-making, how does this guideline recommendation affect patients?

Well, the panel strongly believes that the tailored decision-making process is key in the decision to recommend extended adjuvant therapy. So tailoring on disease factors plays a role in the recommended duration of therapy. Obviously, since we stratified by high-risk and low-risk and what treatment's been received specifically. And if a woman's had bilateral mastectomy, she's not going to benefit from the risk reduction that's achieved with giving somebody extended therapy.

But in addition to disease factors, patient preferences and tolerance of therapy should inform clinician and patient decision-making. Again, since none of the studies have shown improvement in overall survival with longer duration of AI therapy, patients and their medical providers need to make decisions based on an awareness that the benefits include, specifically prevention of distant recurrence and prevention of second breast cancers. And the importance of those benefits is going to vary according to a patient and how she views her life going forward and how bad her side effects have been, how well she tolerates the therapy.

From my own personal point of view, as a breast oncologist, I believe two things. Number one, we should provide aggressive support for managing symptoms in patients who are most likely to benefit from extended therapy. That is, we should not stop therapy early if she is very likely to benefit if we haven't maximized control of her symptoms. There are many things we can do to improve symptoms and we shouldn't just stop therapy because she's not tolerating treatment if we haven't done the most that we can to improve her quality of life and her symptoms.

Conversely, my hope is that we are not doggedly persisting in recommending prolonged therapy in a patient who has a fear of recurrence but who has little to gain from extended therapy. In the latter case, high quality information support is more therapeutic than extended therapy with a medication that's proven, in randomized controlled trials and in her own personal experience, to decrease her quality of life with marginal, if any, medical benefit.

Thank you so much for the overview of this guideline today and thank you for your time.

Thank you.

And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

Feb 20 2019
12 mins
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Rank #20: Self-Evaluation: Soft-Tissue Sarcomas-Epidemiology

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Dr. Arun Singh, Co-Clinical Director of UCLA Sarcoma Clinic and Assistant Professor of Hematology and Oncology at UCLA, presents a self-assessment question from an ASCO University course focusing on the treatment of non-small cell lung cancers.

Feb 27 2019
4 mins
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