Abstract PS13-33: Feasibility of a comprehensive monitoring protocol for the prevention and treatment of interstitial lung disease in patients undergoing treatment with fam-trastuzumab deruxtecan

Background: Fam-trastuzumab deruxtecan (DS-8201) was recently approved in patients with advanced/metastatic HER2 positive breast cancer who have received two or more prior HER2-based regimens. In DESTINY-Breast01, an unprecedented response rate was observed in 61% of heavily pretreated patients; however, all-grade interstitial lung disease (ILD) developed in almost 14% of patients, which led to death in 2% of patients. Additionally, patients with a medical history of clinically significant lung disease were excluded which is not consistent with the standard community patient population that may receive fam-trastuzumab deruxtecan. Currently, there are no recommended protocols in place or guidance for monitoring patients for interstitial lung disease/pneumonitis while on fam-trastuzumab deruxtecan. This is a retrospective chart review to assess the feasibility of implementing an ILD monitoring protocol in a cohort of patients receiving treatment with fam-trastuzumab deruxtecan at the Duke Cancer Institute. Methods: Patients with HER2-positive or HER2-low metastatic breast cancer who received ≥five cycles of fam-trastuzumab deruxtecan between Jan 1, 2020-June 30, 2020 were included. Chest imaging and pulmonary function testing with diffusing capacity for carbon monoxide (DLCO) were performed at baseline prior to initiation and every six weeks prior to cycle 3 and cycle 5 of fam-trastuzumab deruxtecan to monitor for ILD. DLCO was corrected for hemoglobin. Patients that experienced more than a 10% decrease in corrected DLCO (DLCOc) were recommended to have a pulmonology consult in which DLCOc was reviewed in combination with chest imaging and clinical history to evaluate for ILD and recommend continuance or cessation of the drug. Clinical pulmonary symptoms to include cough, shortness of breath, dyspnea, and new or worsening respiratory symptoms were monitored per chart review. Results: Seven patients with HER2-positive (N=6) and HER2-low (N=1) metastatic breast cancer were monitored per predefined ILD monitoring protocol with 100% completion of chest imaging and pulmonary function testing at baseline and prior to cycle 3 and cycle 5 indicating feasibility. There were no confirmed cases of ILD/pneumonitis within the patient cohort. Two patients (28.6%) experienced DLCOc decreases >10% warranting a pulmonology consult. Upon further assessment, ILD/pneumonitis was ruled out based on chest imaging and/or asymptomatic presentation and both patients continued therapy without treatment delay or development of pneumonitis to date. Both patients with DLCOc decrease >10% had a history of lung disease or significant metastatic disease involvement including asthma and lymphangitic carcinomatosis, respectively. In these patients, DLCOc, imaging and clinical history were able to safely rule out ILD. . Conclusion: Implementation of a comprehensive protocol to monitor and assess for ILD associated with fam-trastuzumab deruxtecan is feasible for patients receiving this therapy and may prevent treatment delay in patients with suspected ILD. In this small cohort, stable DCLOc suggests the absence of ILD onset in patients treated with fam-trastuzumab deruxtecan. DLCOc monitoring may be a reasonable measure to assess for ILD-related changes in patients. Further data collection is underway to understand the value of a comprehensive ILD monitoring protocol. Citation Format: Heather Moore, Scott Shofer, Amy Guisinger, Gloria Broadwater, Jeremy Force, Sarah Sammons, Carey Anders, Kelly Westbrook. Feasibility of a comprehensive monitoring protocol for the prevention and treatment of interstitial lung disease in patients undergoing treatment with fam-trastuzumab deruxtecan [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-33.