Abstract P1-11-05: Provider perceptions of DESTINY-Breast04, HER2-low directed treatment, and interstitial lung disease
Authors: Leon Brooke , Bone Robert , Jeune-Smith Yolaine , Feinberg Bruce 
Published: March 2023

Background: Human epidermal growth factor receptor 2 (HER2)-targeted therapies are an established treatment for patients with HER2-positive breast cancer, however, these therapies have not proven effective in the HER2-negative setting. Until recently, HER2 status was used to guide treatment decisions based on a binary classification of positive or negative. A new pathological category, HER2-low, has emerged as a subtype of interest within the breast cancer treatment landscape. HER2-low status is defined as a HER2 immunohistochemistry score of 1+ or 2+ and a negative in-situ hybridization result. DESTINY-Breast04 (DB04) was the first trial to evaluate a HER2-targeted agent within the metastatic HER2-low breast cancer setting. The anti-HER2 agent trastuzumab deruxtecan (T-DXd) demonstrated promising clinical activity in HER2-low expressing tumors. However, development of T-DXd-related interstitial lung disease (ILD) remains a concern when using this therapy. This survey-based study aimed to evaluate community oncologists’ perceptions of the DB04 data, HER2-low directed treatment, and management of ILD. Methods: U.S.-based oncologists (n=83) convened at two live meetings in June 2022 to review clinical updates presented at ASCO 2022. Participant characteristics and demographic data were collected via an online survey prior to the respective meetings. Perceptions/reactions to clinical updates were captured in real-time via electronic keypad. Data were summarized using descriptive statistics. Results: Among respondents, 83.1% identified as community providers, with an average experience of 20.7 years in practice. On average, participants reported that 88.2% of their time is allocated towards direct patient care, with roughly 18 patients seen per clinic day. Nearly half of respondents (49.4%) reported awareness of HER2-low as a distinct pathological category prior to the presentation of DB04 at ASCO 2022, however, less than 10% of respondents had previously used this sub-category to determine therapy. Increased T-DXd-related ILD, which occurred in 12% of trial participants, was cited as the greatest limitation of the DB04 trial by over one-third (37.3%) of respondents. After reviewing real-world evidence data of ILD incidence in metastatic breast cancer, nearly one-third (31%) of respondents reported that their observed ILD rates are less than DB04, but more (36%) said that ILD can be hard to quantify because patients are not always symptomatic. When asked if the ILD rate associated with T-DXd would limit their selection of this agent for their patients with breast cancer, approximately one-quarter (24.1%) of respondents indicated that they would reserve T-DXd use for patients without symptomatic pulmonary disease. However, the majority of respondents (60.2%) indicated that they would not limit their use of T-DXd based on ILD rates, with most (55.4%) opting for a risk-management approach involving increased monitoring for the development of ILD-related adverse events. Conclusions: Advancements in assay interpretation have made it possible to differentiate gradients of HER2 expression, creating a space for pathological sub-categories within a formerly binary paradigm. Among providers who reported awareness of HER2-low as a distinct pathological sub-category, few had used this as a benchmark to guide their treatment decisions prior to the presentation of DB04 at ASCO 2022. Newer anti-HER2 agents, such as T-DXd, provide a potential new standard of care for patients with HER2-low expressing tumors. Despite the concern of ILD rates associated with T-DXd use, the majority of providers do not view this as a limiting factor due to the ability to closely monitor patients for the development of adverse events coupled with appropriate provider/patient education.

Citation Format: Brooke Leon, Robert Bone, Yolaine Jeune-Smith, Bruce Feinberg. Provider perceptions of DESTINY-Breast04, HER2-low directed treatment, and interstitial lung disease [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-05.