Dr D'Abreo on Patient Consideration When Choosing Treatments in HER2+ Breast Cancer

Nina D'Abreo, MD, assistant professor, Department of Medicine, New York University Grossman School of Medicine, chief, Division of Hematology and Medical Oncology, Perlmutter Cancer Center, discusses the importance of considering a patient’s medical history and preferences when deciding on a treatment course in HER2-positive breast cancer and highlights the important role of surgeons within breast cancer treatment.

When selecting treatments for patients with HER2-positive breast cancer, the foremost consideration is understanding the patients’ disease profiles and past toxicities they may have experienced, D'Abreo begins. For example, a patient with prior taxane exposure and residual neuropathy might face challenges with a full course of ado-trastuzumab emtansine (T-DM1; Kadcyla) due to underlying neuropathy, she emphasizes. Patient preferences, such as an aversion to alopecia, is also crucial to consider, D’Abreo says.

Familiarity with the drugs’ toxicity profiles and thorough advance knowledge of the patient are essential, she expands. Patients with prior radiation and underlying lung issues may not be ideal candidates for fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and may require closer monitoring, D’Abreo notes. Close monitoring, in addition to safety data, has played a significant role in minimizing toxicity, evident from the advancements with T-DXd made in the DESTINY suite of trials, she explains, adding that vigilance regarding lung toxicity, for example, is vital to ensuring patients receive the full benefit from this agent.

Furthermore, in the treatment of these patients, surgeons play a pivotal role in disease management, and can be integrated into treatment decision making through multidisciplinary conferences, D’Abreo continues. With the introduction of neoadjuvant therapy, logical responses guide the assessment of therapy efficacy, she says. Surgeons contribute significantly by identifying the patients who meet neoadjuvant therapy criteria and swiftly proceeding to surgery to assess pathologic complete response, D’Abreo emphasizes. Educating surgeons about treatment criteria and informing them of available neoadjuvant trials is essential, she adds. Surgeons are the primary point of contact for many patients, and their awareness of available trials facilitates patient education. The early involvement of surgeons in treatment decision making has proven to be a valuable asset, D’Abreo concludes.

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Nina D'Abreo, MD, discusses the importance of considering a patient’s medical history and preferences when deciding on a treatment course in HER2-positive breast cancer and highlights the important role of surgeons within breast cancer treatment.


Dr D'Abreo on the Evolution of ADC Use in the HER2+ Breast Cancer Treatment Landscape

Nina D'Abreo, MD, assistant professor, Department of Medicine, New York University Grossman School of Medicine, chief, Division of Hematology and Medical Oncology, Perlmutter Cancer Center, discusses the evolution of antibody-drug conjugates (ADCs) in the treatment of patients with HER2-low or HER2-positive breast cancer.


ADCs have become a prominent option in the current breast cancer treatment landscape, and represent a key advancement in breast cancer care, D'Abreo begins. Strategic deployment of these ADCs is vital to optimize their impact, not only in advanced stages of breast cancer but also in the early disease stages, D’Abreo. This includes both neoadjuvant and adjuvant settings, she adds. Innovative combinations of ADCs and oral therapies are currently being explored and are of particular interest in adjuvant settings. The phase 3 CompassHER2 RD trial (NCT04457596) is one such study of adjuvant ado-trastuzumab emtansine (Kadcyla; T-DM1) plus placebo vs T-DM1 and tucatinib (Tukysa) in this space, D'Abreo notes.

Additionally, there is a notable shift towards chemotherapy-free approaches in breast cancer. This is exemplified by ongoing trials of regimens minimizing or entirely excluding cytotoxic therapies through the inclusion of ADCs, she expands. A pivotal aspect in these trials is the meticulous process of patient selection, D'Abreo says. Translational medicine plays a crucial role in identifying individuals who benefit from these trials using tools such as genomics, she emphasizes. Some trials have already utilized these assays.

Radiology also emerges as a valuable tool in aiding treatment decision-making, she continues. The focus is now on discerning intrinsic subtypes, which can identify the patients who may gain the most from these chemotherapy-free alternatives, D'Abreo imparts. The evolving landscape in breast cancer underscores the notion that a one-size-fits-all approach is outdated, she emphasizes. Instead, the field is focused on tailoring treatments, minimizing toxicity, and optimizing therapeutic interventions for patients deserving access to specific biological tools in addition to traditional PCR, she explains. This dynamic approach holds promise and marks an exciting phase in the field, D'Abreo concludes.

Nina D'Abreo, MD, discusses the evolution of antibody-drug conjugates in the treatment of patients with HER2-low or HER2-positive breast cancer.


Dr D'Abreo on Leveraging Biology When Treating HER2+ Breast Cancer

Nina D'Abreo, MD, assistant professor, Department of Medicine, New York University Grossman School of Medicine, chief, Division of Hematology and Medical Oncology, Perlmutter Cancer Center, discusses her presentation from an 

® State of the Science Summit™ on breast cancer, during which she discussed the treatment of patients with HER2-low and HER2-positive breast cancer.

The transformative advancements in the treatment of patients with HER2-positive cancer have presented oncologists with the challenge of effectively utilizing the wealth of available data, she begins. In D'Abreo’s presentation, she emphasized 3 key aspects for tailoring treatment for patients with early-stage HER2-positive breast cancer: leveraging biology, considering clinical risk factors, and prioritizing patient safety in terms of toxicity.

Addressing clinical risk involves considering traditional disease factors, such as tumor size and lymph node status, supported by pertinent data, D'Abreo expands. Biological risks include genomic risks, which can be measured through the radiological assessment of PCR results and offer predictive insights regarding which patients may respond to which treatments, she states. Significantly, toxicity considerations encompass adverse effects (AEs), financial implications, and time-related challenges, emphasizing the need for a holistic approach to patient care, D'Abreo notes.

When oncologists are faced with a multitude of treatment options, D’Abreo says it is important to consistently prioritize 2 equally significant aspects. Firstly, evidence is crucial as oncologists aim to achieve the best outcomes for patients. For example, for patients with residual disease in the adjuvant setting, the effectiveness of antibody-drug conjugates, such as ado-trastuzumab emtansine (T-DM1; Kadcyla) and fam-trastuzumab deruxtecan-nxki (Enhertu) is well established, leading to a shift away from using trastuzumab (Herceptin) and pertuzumab (Perjeta), as supported by robust data from the phase 3 KATHERINE trial (NCT01772472), she elucidates.

Although improving patient outcomes is imperative, equally crucial is considering the toxicity implications of available therapies, D'Abreo notes. Plans to treat a patient with an effective agent, such as TDM-1, may be hindered if a patient experiences AEs, such as significant neuropathy. Thus, the treatment decision-making process involves carefully assessing the toxicity profiles of individual drugs. Overall, both the strength of efficacy evidence and the potential for toxicity play pivotal roles in guiding breast cancer treatment choices, ensuring a comprehensive treatment approach that prioritizes both efficacy and patient well-being, D'Abreo concludes.

Nina D'Abreo, MD, discusses advances made in the treatment of patients with HER2-low and HER2-positive breast cancers.

Nina D'Abreo, MD, assistant professor, Department of Medicine, New York University Grossman School of Medicine, chief, Division of Hematology and Medical Oncology, Perlmutter Cancer Center, discusses the integration of HER2-directed antibodies and targeted therapies into the treatment armamentarium for patients with HER2-positive breast cancer.

Since the early stages of examining adjuvant therapies for patients with HER2-positive breast cancer, there has been a shift in treatment approaches because of the introduction of HER2-directed antibodies, as well as the introduction of targeted therapies, D'Abreo begins. HER2-directed antibodies have redefined the way oncologists address treatment decisions for patients with HER2-positive breast cancer, she explains, adding that these agents have positively affected the prognosis of patients with this disease. These agents’ role primarily involves complementing or augmenting traditional chemotherapy, which still serves as the fundamental component of standard HER2-targeted treatment regimens, D'Abreo explains.

At present, the oncology landscape is advancing toward a more nuanced cancer management strategy that seeks to leverage the advantages of chemotherapy alongside the antibodies and antibody-drug conjugates (ADCs) that have been introduced into this domain, D'Abreo expands. Rather than merely enhancing traditional chemotherapy agents with HER2-directed antibodies, the field is exploring the potential for replacing or substituting these agents with ADCs in select cases, she states. Notably, it is important to understand that there are also targeted therapies available that operate in the HER2 downstream signaling pathway, including TKIs and orally administered HER2 inhibitors, D'Abreo says. These targeted therapies that are now being introduced into the treatment landscape include agents such as fam-trastuzumab deruxtecan-nxki (Enhertu).

Consequently, the breast cancer field is actively investigating opportunities to synergize chemotherapy with these novel treatments for certain patients, D'Abreo continues. Simultaneously, there is a growing interest in the potential to replace chemotherapy with non-chemotherapeutic alternatives in specific instances, emphasizing the versatility and evolution of the therapeutic approaches available for patients with HER2-positive breast cancer, D'Abreo concludes.

Nina D'Abreo, MD,

Articles

Dr D'Abreo on Patient Consideration When Choosing Treatments in HER2+ Breast Cancer

Dr D'Abreo on the Evolution of ADC Use in the HER2+ Breast Cancer Treatment Landscape

Dr D'Abreo on Leveraging Biology When Treating HER2+ Breast Cancer

Dr D'Abreo on HER2-Targeted Therapies in HER2+ Breast Cancer