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Patt Highlights Payer, Education Considerations in Trastuzumab Deruxtecan Use for HER2-Low Breast Cancer

Evidence-Based OncologyPatient-Centered Oncology Care 2022
Volume 29
Issue 3
Pages: SP207

At Patient-Centered Oncology Care®, Debra Patt, MD, PhD, MBA, of Texas Oncology, discussed managed care considerations that arise from the groundbreaking DESTINY-Breast04 study presented earlier this year.

Note: A previous version of this article appeared with our meeting coverage.

Months after the findings brought a standing ovation at the American Society of Clinical Oncology (ASCO) annual meeting, results from DESTINY-Breast04 (NCT03734029) continue to make waves in breast cancer care.

They also raise considerations for payers and a need for education among doctors, according to Debra Patt, MD, PhD, MBA, executive vice president of Texas Oncology, who offered the remarks during the 2022 meeting of Patient-Centered Oncology Care®.

Patt, speaking in Nashville, Tennessee, for the annual event presented by The American Journal of Managed Care®, highlighted the dramatic responses seen with trastuzumab deruxtecan in the trial. The risk of disease progression or death fell 50% compared with chemotherapy for human epidermal growth factor receptor-2 (HER2)-low patients with both hormone receptor (HR)-positive and HR-negative disease.1 Sold as Enhertu by AstraZeneca, the therapy received FDA approval for this indication on August 6, 2022, just 2 months after the ASCO presentation.2

Practice-changing results that affect so many patients require shifts for providers and payers, Patt explained. These results are a leap forward that will help achieve the dual goal of cancer control with less toxicity than prior treatments. This allows a physician “to meet patients where they are and to make sure that not only [can] they benefit from control of their cancer, whether that’s cure control, like a chronic disease, but also [that they can] be in their communities, so they can work at their jobs and sleep in bed next to their spouse and be at their dinner tables, and…pick their kids up from soccer,” Patt said. “I’m really passionate about that.”

How it works. Trastuzumab deruxtecan works in a disease classification not previously appreciated by pathologists or physicians, but one that could cover just over half of all patients with metastatic breast cancer. “It’s this unmet clinical need,” Patt explained.

Under the previous standard of care, there were different therapeutic choices depending on a patient’s HR profile or BRCA mutation status, but all paths led to chemotherapy.

“As we all know, traditional cytotoxic chemotherapy is a really effective tool as we treat cancer. But it’s a blunt instrument that kills cells that are rapidly dividing, that has a lot of associated toxicities,” she said. “A universal axiom that we’ve learned as we get more specific in targeted therapies is that the more specific the target is, …the less toxicity on average.”

Patt explained how the antibody-drug conjugate trastuzumab deruxtecan works: it targets HER2 by going inside the cell with a cleavable linker, and then releases its topoisomerase inhibitor payload. This “leaks” to nearby cells in what has been called a “bystander” effect.

Dramatic outcomes. Trial results showed a 50% improvement in progression-free survival and a 36% improvement in overall survival compared with traditional chemotherapy. Results were consistent across subgroups, including patients previously treated with CDK4/6 inhibitors.
The findings establish trastuzumab deruxtecan as the new standard of care for patients with HER2-low metastatic breast cancer (immunohistochemistry [IHC] 1+ and IHC 2+/fluorescence in situ hybridization [FISH] negative). But this creates some new challenges, Patt noted.

Finding the patients. Before DESTINY-Breast04, traditional classification of patients with breast cancer did not include HER2-low disease; now IHC testing protocols may shift. “This is where we really need payer and provider collaboration,” she said.

Often, FISH testing that checks for extra copies of the HER2 gene was the norm, with IHC only done if specifically requested. Today, Patt said, all patients with localized and metastatic breast cancer should receive IHC testing with FISH completed per ASCO/College of American Pathologists guidelines. This has required educating some communities about the need for IHC.

Further, in some cases archived tissue must be retrieved and retested. “So there was a logistical challenge, in that pathology groups are experiencing many of the same challenges that we experience today in clinic with staffing. These things that would usually take days might take weeks [and] sometimes took months,” she said. “It’s never an acceptable answer to tell a patient that they need another biopsy because you can’t get the pathology group…staff to repeat testing on a specimen.”

So far, Patt has not run into challenges with payer coverage for testing. What worries her more? It’s clinicians not ordering the appropriate testing because they are so worried about the false negatives they might see, and they may not identify potential therapeutic opportunities. “It’s really important to talk about that,” she said.

Adverse effects. Nausea is still a challenge. Patt said her clinic has changed its antiemetic protocols to reflect highly emetogenic chemotherapy. “It’s an important intervention for patients on this therapy,” she noted, adding that taking steps to prophylaxis nausea is appropriate.

“Neutropenia can happen, but it’s uncommon,” she said. Interstitial lung disease has been seen, but physicians are better now at evaluating patients at the sign of a cough.

Patt addressed alopecia, which occurs in 30% of patients, and her clinic manages successfully with cold-capping. “I’m from the great state of Texas and we love our big hair,” she said, then added a serious note: “For women, controlling alopecia is important…. I certainly participate in advocacy to try to get favorable coverage [of treatments for alopecia].”

It goes back to her commitment to allowing patients to live their lives, she said.

“To be able to go and pick up your kids from school and not have their best friends ask, ‘What’s wrong with Mommy?’ because she doesn’t have her hair is really meaningful and helps manage this for families and for patients.” 


1. Modi S, Jacot W, Yamashita J, et al; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
2. Caffrey M. Trastuzumab deruxtecan wins rapid approval for HER2-low breast cancer. The American Journal of Managed Care®. August 6, 2022. Accessed January 6, 2023. https://www.ajmc.com/view/trastuzumab-deruxtecan-wins-rapid-approval-for-her2-low-breast-cancer

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