Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer Guideline Update

An interview with Dr. Neelima Denduluri from Virginia Cancer Specialists, U.S. Oncology in Arlington, VA and Dr. Sharon Giordano from the University of Texas MD Anderson Cancer Center in Houston, TX on "Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update." This update addresses the use of adjuvant trastuzumab emtansine and the use of biosimilar forms of trastuzumab. 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 podcast.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Neelima Denduluri from Virginia Cancer Specialists, US Oncology in Arlington, Virginia, and Dr. Sharon Giordano from the University of Texas M.D. Anderson Cancer Center in Houston, Texas, co-chairs on "Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update."

Thank you for being here, Dr. Denduluri and Dr. Giordano.

Dr. Neelima Denduluri: Thanks for having us.

Dr. Sharon Giordano: Yeah, we're delighted to be here. Thank you.

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. Denduluri, do you have any relevant disclosures that are related to this guideline topic?

Dr. Neelima Denduluri: Our institution has received research funding from companies including Genentech.

Brittany Harvey: Thank you. And Dr. Giordano, do you have any relevant disclosures that are related to this guideline topic?

Dr. Sharon Giordano: No, I don't have any relevant disclosures. Thank you.

Brittany Harvey: Thank you. Then let's get into the guideline content. Dr. Denduluri, what prompted this focused update of the selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer guideline?

Dr. Neelima Denduluri: There was an FDA meta analysis and several other studies that showed that patients that did not receive a pathologic complete response after preoperative therapy in the HER2-positive setting had a worse prognosis. In the past, we didn't have actionable findings to improve their outcome.

But there was a trial, the KATHERINE trial, that randomized patients that received chemotherapy and trastuzumab, plus or minus pertuzumab, that did not achieve a pathologic complete response to receive standard of care trastuzumab or 14 cycles of trastuzumab emtansine. And the patients that received trastuzumab emtansine had a significantly improved outcome over those that received standard of care trastuzumab. These were very impactful findings that changed care for women with early breast cancer. Therefore, we wanted to update the guideline.

Brittany Harvey: So Dr. Giordano, there are two new recommendations in this guideline update. First, what does the guideline say regarding the use of adjuvant trastuzumab emtansine following standard preoperative chemotherapy and HER2-targeted therapy for patients with HER2-positive breast cancer with residual invasive cancer in the breast or lymph nodes at surgery?

Dr. Sharon Giordano: So the first recommendation was based on the data from the KATHERINE trial that Dr. Denduluri just mentioned. And so their recommendation is that patients with HER2-positive breast cancer who have pathologic invasive residual disease at surgery to either in the breast or the lymph node after standard pre-op chemo with HER2-targeted therapy should be offered 14 cycles of adjuvant trastuzumab emtansine unless there's a recurrence or unworkable toxicity. So basically stating, based on the data from KATHERINE, that if patients have residual disease after their chemotherapy for HER2-positive breast cancer, they should get adjuvant trastuzumab emtansine. And the panel overall felt that the evidence behind this-- the quality of the evidence was very high, and it had a strong recommendation for this treatment.

Brittany Harvey: And then second, Dr. Denduluri, how does this guideline address the use of biosimilar forms of trastuzumab?

Dr. Neelima Denduluri: So biosimilars are increasingly being incorporated into clinical practice, and the guidance that we have from the FDA is that the efficacy of biosimilars compares well with standard trastuzumab. So, we said that patients that would receive trastuzumab are allowed to receive trastuzumab biosimilar without what we think will negatively impact their outcome.

Dr. Sharon Giordano: For that recommendation, we also had input from the Breast Cancer Guideline Advisory Group that helped us decide to expand the update to include the biosimilars. We think that at least five biosimilars have been approved by the FDA, and based on similar efficacy and similar safety data felt that it was appropriate to use them or trastuzumab in a setting where previously we had just used trastuzumab.

Brittany Harvey: Great. And then how will this guideline update impact clinical practice?

Dr. Sharon Giordano: I think that many practitioners have already adapted clinical practice to start to use adjuvant trastuzumab emtansine based on the KATHERINE data, but we certainly hope that this guideline update will reinforce the practice of providing adjuvant trastuzumab emtansine for patients with HER2-positive breast cancer with residual disease after preoperative treatment. The improvement in outcomes was really clinically meaningful for patients, so this does seem to be a significant step forward in the treatment of HER2-positive breast cancer.

Dr. Neelima Denduluri: Additionally, I think that it's important to remember, as clinicians, that we should think about preoperative therapy in those patients with higher-risk HER2-positive disease, because we know that we can impact their outcomes if they don't achieve a pathologic complete response. And hopefully this guideline will heighten the awareness that we need to do that. The other question that we commonly are asked is, even if there is a small amount of residual invasive carcinoma, should we switch to trastuzumab emtansine instead of trastuzumab plus or minus pertuzumab. And what the KATHERINE data did show is that patients that-- even if they had a small amount of residual cancer burden, they still derived benefit.

Obviously, we have to think about the safety, and we also wanted to outline that in this guideline that trastuzumab emtansine is associated with a higher risk of neuropathy and thrombocytopenia and liver function abnormalities. So we certainly need to worry about that. And those patients that do have poor tolerance, we can go back to their HER2-targeted backbone they received in the preoperative setting.

Dr. Sharon Giordano: Yeah, those are great additional points.

Brittany Harvey: Definitely. And you've both already touched on a bit of how adjuvant therapy impacts patients, but how will these guideline recommendations affect patients?

Dr. Neelima Denduluri: I think that really, as Dr. Giordano stated, this is an overwhelming benefit that we don't normally see in terms of impacting outcomes. So the addition of trastuzumab emtansine potentially has good efficacy for them and improves their outcomes.

Dr. Sharon Giordano: Yeah, I agree. I think this trial was associated with a really meaningful reduction in risk of recurrence and better outcomes. So this really is a step forward for treating HER2-positive breast cancer.

Dr. Neelima Denduluri: The other interesting thing about this trial is that it did not delay their local therapy. They allowed concurrent trastuzumab emtansine with radiation therapy. And they also, in terms of systemic therapy, allowed endocrine therapy with trastuzumab emtansine, similar to what we do with trastuzumab plus or minus pertuzumab in the adjuvant setting. So as Dr. Giordano stated, really impactful in terms of efficacy, well-tolerated in most situations, and pragmatic in terms of not holding up the local therapy and the systemic therapy that they may need additionally.

Brittany Harvey: Great, thank you so much for sharing that information about how it impacts patients. I appreciate you both coming on the podcast today and for all your work that you put into updating these guidelines. And thank you for your time today Dr. Giordano and Dr. Denduluri.

Dr. Sharon Giordano: Thank you so much. It was a pleasure.

Dr. Neelima Denduluri: Thank you both, and thank you Brittany for always working so hard to make sure that these guidelines help our patients.

Brittany Harvey: 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. 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.