Chemotherapy and Targeted Therapy for Patients with Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor-Negative Guidelin

An interview with Dr. Beverly Moy from Massachusetts General Hospital, co-chair on “Chemotherapy and Targeted Therapy for Patients With HER2-Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor-Negative: ASCO Guideline Update.” Updated guidance addresses optimal sequence of therapy & indications for treatment regimens. Read the guideline at asco.org/breast-cancer-guidelines. Suggest a topic for guideline development at surveymonkey.com/r/ascoguidelinesurvey.   TRANSCRIPT [MUSIC PLAYING] SPEAKER: 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. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org. My name is Brittany Harvey. And today I'm interviewing Dr. Beverly Moy from Massachusetts General Hospital in Boston, Massachusetts, co-chair and lead author on chemotherapy and targeted therapy for patients with HER2 negative metastatic breast cancer that is either endocrine pre-treated or hormone receptor negative ASCO guideline update. Thank you for being here, Dr. Moy. BEVERLY MOY: Thanks for having me, Brittany. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Moy, do you have any relevant disclosures that are directly related to this guideline topic? BEVERLY MOY: I do not have any relevant disclosures related to this guideline topic. BRITTANY HARVEY: Great. Thanks so much. Then let's get into what this update covers. So first, what prompted the update of this ASCO guideline and what does the scope of this guideline update? BEVERLY MOY: So this guideline update was developed to address both chemotherapy and targeted therapy for women with advanced HER2 negative breast cancer that is either endocrine pre-treated or hormone receptor negative. So it really focuses on chemo and targeted therapy. The original ASCO clinical treatment guideline was published in 2014 and really focused on chemotherapy, since that was generally the standard of care at that time. Since 2014, however, there have been several important new therapies that have become available based on robust evidence from numerous clinical trials. These include, but are not limited to, BOLERO-6 and PEARL trials for hormone receptor positive HER2 negative metastatic breast cancer, the ASCENT and EMBRACE trials for triple negative metastatic breast cancer, and the EMBRACA trial for metastatic breast cancer associated with germline BRCA1 or 2 mutations. So it really was important to update the guideline in a fairly urgent matter. BRITTANY HARVEY: Great. Well, then this guideline addresses four overarching clinical questions. For each of these, I'd like to review the key recommendations for our listeners. So starting with question one, is there an optimal sequence of chemotherapy and/or targeted therapy for patients with triple negative metastatic breast cancer either with or without BRCA1 or BRCA2 germline mutations? BEVERLY MOY: So clinical question one really focused on patients with metastatic triple negative breast cancer. So for patients with metastatic triple negative disease, the first key question is, what is the Programmed cell Death Ligand 1, or what we call PD-L1 status? If the disease is PD-L1 positive, then patients may be offered first line therapy with an immune checkpoint inhibitor plus chemotherapy. And that's a very important development. If the disease, however, is PD-L1 negative, patients should be offered single agent chemotherapy rather than combination chemotherapy, unless they have symptomatic or immediately life-threatening disease, and you really need to get a response more quickly. In those cases, combination chemotherapy can be used. After the first line, if patients with metastatic triple negative breast cancer have received at least two prior therapies, then they should be offered treatment with the new antibody drug conjugate called sacituzumab govitecan, which is a very exciting development in the treatment of metastatic triple negative breast cancer. If the patient has a germline BRCA1 or 2 mutation and has metastatic triple negative disease and have been previously treated with chemotherapy, then they may be offered treatment with an oral PARP inhibitor rather than chemotherapy, also a very exciting development that this guideline update addresses. BRITTANY HARVEY: Great. Thank you for reviewing those recommendations for triple negative metastatic breast cancer. So then next for clinical question two, what are the indications for chemotherapy versus endocrine therapy in endocrine pre-treated estrogen receptor positive metastatic breast cancer? BEVERLY MOY: So clinical question two focuses on women or patients with metastatic hormone receptor positive breast cancer who have developed progressive disease on a prior endocrine therapy with or without targeted therapy. So really is focusing on patients with metastatic hormone receptor positive breast cancer that have become fairly resistant to endocrine therapy alone. These patients may be offered treatment with either endocrine therapy with or without a targeted therapy or single agent chemotherapy. Brittany, I think it's important for listeners to realize that there is another important clinical practice guideline update that's being released simultaneously with this guideline. And that one is called endocrine therapy and targeted therapy for hormone receptor positive metastatic breast cancer. This other guideline update will describe in detail recommendations for the various targeted therapies that can be used with endocrine therapy, such as CDK4/6 inhibitors, PI 3-kinase inhibitors, and others. So I encourage everyone to read this guideline as well. Importantly, both guidelines state that treatment choice should be based on individualized patient and provider assessment of preferences, risks, and benefits. BRITTANY HARVEY: Great. And thank you for pointing out that companion guideline. Listeners can also listen to a podcast episode with Dr. Burstein on that particular guideline, which will be available in our podcast feed. So then next, what are the key recommendations for the third question in the guideline, which is, is there an optimal sequence of non-endocrine agents for patients with hormone receptor positive but HER2 negative metastatic breast cancer who are no longer benefiting from endocrine therapy, either with or without BRCA1 or BRCA2 germline mutations? BEVERLY MOY: So this third question really focuses on patients with hormone receptor positive HER2 negative disease and the optimal sequence. Essentially what we recommend is that germline BRCA1 or 2 patients with metastatic hormone receptor positive HER2 negative breast cancer who are no longer benefiting from endocrine therapy, those patients may be offered an oral PARP inhibitor in the first through third line setting rather than chemotherapy. And that is evidence that is evolving and important, and that's what the guideline recommends at this time. BRITTANY HARVEY: Great. And then clinical question four was the last question addressed in this guideline update. And what did the panel say regarding at what point should a patient be transitioned to hospice or best supportive care only? BEVERLY MOY: So this obviously is an incredibly important question for clinicians and oncologists to consider. The current literature and evidence does not allow us, at this time, to make a firm recommendation regarding at which point a patient's care should be transitioned to hospice or best supportive care only. When to transition is a decision that really needs to be shared between the patient and clinician in the context of an ongoing conversation regarding goals of care. The conversation of that integration of supportive care and eventual consideration of hospice care really should start early in the management of metastatic breast cancer. And these conversations have to occur throughout. I would also refer listeners to other important clinical treatment guidelines on the ASCO website about incorporation of palliative and supportive care for patients with metastatic cancer. I think those are incredibly valuable guidelines. BRITTANY HARVEY: And then you've touched on this a bit as you've talked about the recommendations, but in your view, what is the importance of this guideline update? And how will these updated recommendations impact both clinicians and patients? BEVERLY MOY: I think that this is an extremely important guideline update. It provides really important clinical guidance about the new use of immune checkpoint inhibitors, which really is the first time immune checkpoint inhibitors are clearly recommended for the treatment of breast cancer. It also provides important clinical guidance about this new antibody drug conjugate, sacituzumab govitecan, and PARP inhibitors for the treatment of metastatic breast cancer. These are all important and effective new treatments for breast cancer. And every clinician should be aware of their optimal uses. I will point out that many unanswered questions remain. And that was really an exciting part of doing this guideline update to look at these unanswered questions, such as what we described earlier, the optimal time to transition to best supportive care only and the widespread use of molecular tumor profiling. As treatments get more complicated and the entire oncology community are increasingly tasked to absorb new data, ASCO guidelines are enormously helpful in giving people an easy to access tool that takes into account the latest data. BRITTANY HARVEY: Great. Thank you so much for your work on this guideline update and for taking the time to speak with me today, Dr. Moy. BEVERLY MOY: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast cancer guidelines. Additionally, our annual survey for guideline topics is open for submissions. Suggest a topic for guideline development at surveymonkey.com /r/ascoguidelinesurvey. The link is also available in the episode notes of this podcast. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss episode. [MUSIC PLAYING]