Presenting Authors: Jennifer A. Hutchinson, PharmD, BCOP, and E. Bridget Kim, PharmD, BCPS, BCOP, Massachusetts General Hospital, Boston, MA
Co-Authors: Lily Jia, PharmD, BCOP, Beth Israel Deaconess Medical Center, Boston, MA; Christina Jacob, PharmD Candidate, Massachusetts General Hospital, Boston, MA; Allison Bicker, PharmD Candidate, Massachusetts General Hospital, Boston, MA
BACKGROUND: Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody-drug conjugate currently approved for metastatic HER2+ and HER2-low breast cancer, HER2-mutant non–small cell lung cancer, and HER2+ gastric cancer. Although the adverse events of T-DXd are generally manageable, clinical trials showed increased rates of interstitial lung disease (ILD), with an overall incidence up to 15.4% across all disease states, 3.5% of which were grade ≥3. Given its novel mechanism of action and expanding use in practice, a better understanding of ILD monitoring and management is necessary to ensure patients fully benefit from T-DXd.
OBJECTIVE: To examine the incidence, severity, and management of ILD in patients receiving T-DXd compared with clinical trials.
METHODS: This study was a retrospective chart review of patients who have received ≥1 dose of T-DXd at Massachusetts General Hospital or Beth Israel Deaconess Medical Center between December 2019 and February 2023. Patients aged ≥18 years with a diagnosis of breast, gastric, or lung cancer were included. The primary outcome was the incidence of ILD. The secondary outcomes included the timing and severity of ILD based on the Common Terminology Criteria for Adverse Events and management strategies for confirmed ILD.
RESULTS: A total of 126 patients (breast cancer, 80%; gastric cancer, 11%; lung cancer, 9%) were included in this multicenter, retrospective review. The median number of T-DXd doses received was 6 (range, 1-50 doses), with a median treatment duration of 126 days (range, 0-1085; interquartile range [IQR], 46-193). The overall incidence of confirmed ILD was 5.6%, with 1 patient (4%) having a grade ≥3 event. The median time to the first incidence of ILD was 81 days (range, 1-273; IQR, 52-148), with a median time to resolution of 44 days (range, 8-258; IQR, 28-95). ILD was primarily managed with observation (71%), steroids (25%), and supportive care (8%). All 24 patients who had confirmed or possible ILD had ≥1 risk factor; 95.8% had ≥1 previous anticancer therapies with a notable risk for ILD, 79% had previous chest radiation, 29% had a history of smoking, and 25% had a history of lung disease (including ILD).
CONCLUSION: The incidence of T-DXd–associated ILD in this study was less than that reported in clinical trials; however, the severity remained similar. Patients with risk factors for ILD were more likely to have ILD. This study demonstrates the need for increased awareness and monitoring of ILD, particularly in patients with preexisting risk factors for ILD.
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