An interview with Dr. Andrea Eisen from Sunnybrook Odette Cancer Centre and Ontario Health in Toronto, Ontario, co-chair on "Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update." This guideline updates recommendations for which patients with primary breast cancer should be treated with bone-modifying agents, and which bisphosphonates are optimal. Read the full guideline at www.asco.org/breast-cancer-guidelines.

TRANSCRIPT

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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 ASCO.org/podcasts.

My name is Brittany Harvey, and today I'm interviewing Dr. Andrea Eisen from Sunnybrook Odette Cancer Center and Ontario Health in Toronto, Ontario, lead author on "Use of Adjuvant Bisphosphonates and other Bone-Modifying Agents in Breast Cancer," American Society of Clinical Oncology and Ontario Health Cancer Care Ontario Guideline Update. Thank you for being here, Dr. Eisen.

ANDREA EISEN: Thanks very much for the opportunity.

BRITTANY HARVEY: And I'd like to note that ASCO takes great care of 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. Eisen, do you have any relevant disclosures that are directly related to this guideline topic?

ANDREA EISEN: I have no disclosures.

BRITTANY HARVEY: Thank you. Then let's talk about the content of this guideline. So what prompted an update to this guideline published in 2017, and what is the scope of this update?

ANDREA EISEN: So ASCO has a guideline update process which triggers updates and reviews when new data are available. And for this particular guideline, an update was prompted by publication of three randomized trials. And during the update process, a fourth trial was published that was relevant for the guidance document.

BRITTANY HARVEY: Great. That's great background. So then next, I'd like to review the key recommendations of this guideline for each clinical question, starting with, which patients with primary breast cancer should be treated with bone-modifying agents?

ANDREA EISEN: The first recommendation for this guideline is that adjuvant bisphosphonate therapy should be discussed with all postmenopausal breast cancer patients, regardless of their hormone receptor status, or HER2 status, who are candidates to receive adjuvant systemic therapy.

BRITTANY HARVEY: Great. And then what is recommended for which bisphosphonates should be used for breast cancer adjuvant therapy, and what doses, duration of administration, time to initial treatment, and routes are optimal?

ANDREA EISEN: For this question, there were a number of different regimens available for review and inclusion in the guideline, because the studies used several different treatment protocols. However, the guideline recommends that adjuvant bisphosphonates should be started early, and ideally within three months of the definitive surgery or within two months of completion of adjuvant chemotherapy. The options for treatment include oral clodronate, oral ibandronate, or several different dosing regimens of zoledronic acid.

BRITTANY HARVEY: Great. So then you've just mentioned three different bisphosphonates. So what is the role of the bone-modifying agent denosumab as an adjuvant therapy for primary breast cancer?

ANDREA EISEN: This was a difficult, and perhaps the most contentious area that the committee considered, because there are two very important clinical trials that were reviewed. The first, the ABCSG trial, and the second was the more recently published D-CARE study. The guideline committee does not recommend the use of adjuvant denosumab for the prevention of breast cancer recurrence in early stage breast cancer patients.

BRITTANY HARVEY: That's helpful for clinicians to know, both which are recommended and which aren't recommended at this time. So then finally, Dr. Eisen, in your view, what is the importance of this guideline update, and how does it impact both clinicians and patients with cancer?

ANDREA EISEN: There are at least two issues that make this guideline particularly timely and important. First, there's new clinical trial guidance available, in particular with respect to scheduling and dosing of bisphosphonates and route of administration. These data also highlight the benefits of bisphosphonates.

The second is that the new evidence confirms our previous recommendation that denosumab is not recommended as adjuvant treatment in early stage breast cancer patients. During the development of this update, it became apparent that the uptake of adjuvant bisphosphonate usage in breast cancer patients is probably suboptimal. And there is a number of reasons for this across different jurisdictions.

Some reasons include variable access to different formulations of the bisphosphonates. For example, oral clodronate, which is well studied, is not available in the United States. The second issue that was highlighted was variable access for patients with respect to insurance coverage. And we also identified that even in jurisdictions where funding is fully provided for adjuvant bisphosphonates, uptake might be suboptimal.

So we hope that publishing this guideline and reviewing the evidence and highlighting the potential benefits in terms of reduction in recurrence and improvement in survival will result in more utilization of the bisphosphonates. We recognize that there are potential toxicities associated with the treatment and that the benefits versus risks have to be weighed carefully. The guideline committee recommended the utilization of an online risk assessment tool to help in those discussions with patients and to determine which patients have sufficient risk to justify using bisphosphonates.

BRITTANY HARVEY: Great. Those access issues are important to highlight. And I appreciate all of the work that you've done on this guideline update and also for taking the time to speak with me today, Dr. Eisen.

ANDREA EISEN: Thanks very much.

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. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

ANNOUNCER: 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. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.