A39-21 Trastuzumab-Deruxtecan Re-Challenge in Patients With Prior Drug-Induced Pneumonitis

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate used for treatment of metastatic breast cancer. A serious complication is T-DXd-associated pneumonitis. Its severity is defined by Common Terminology Criteria for Adverse Events version 5.0, graded 1 (asymptomatic) to 5 (death). Grade 1 is defined as asymptomatic clinical or radiographic findings not requiring medical intervention, while grade 2 or higher as symptomatic and requiring medical intervention. Current guidelines suggest permanent discontinuation of T-DXd in all patients who develop grade 2 or higher pneumonitis (severe pneumonitis). Limited data exists on the risk of recurrent pneumonitis in patients with severe pneumonitis re-challenged with T-DXd, so T-DXd may be stopped in patients who were having good cancer response. To evaluate this, we investigated the impact of re-challenging patients with severe pneumonitis. We conducted a retrospective study of consecutive breast cancer patients who received T-DXd and developed pneumonitis from 2019 to 2024 at The Ohio State University. Demographics, prior cancer treatment, T-DXd treatment course, progression-free survival (PFS), overall survival (OS), and days from T-DXd re-challenge to recurrent pneumonitis (if applicable) were recorded. We compared those variables in patients who developed severe pneumonitis but re-challenged with T-DXd (non-standard group) versus patients who developed mild pneumonitis (grade 1) and were re-challenged or who developed any pneumonitis but not re-challenged (standard group). Kaplan-Meier survival curves and log-rank tests compared PFS and OS between the two groups. Statistical analysis was performed using R software (version 4.2.2). Twenty-three patients with T-DXd pneumonitis were identified. Among these patients, 6 patients were in the non-standard group while 17 were in the standard group. Six patients had severe pneumonitis and were re-challenged with T-DXd, with 1 developing recurrent pneumonitis. Median PFS was 417 days in standard group and 804 days in the non-standard group (p = 0.55). The difference in OS between the groups was not statistically significant (p = 0.25; see figure). Though there was no statistically significant difference in PFS or OS in patients managed with standard vs non-standard re-challenge of T-DXd, a trend towards improved cancer outcomes was noted in the non-standard group. Only 1 patient experienced recurrent pneumonitis after T-DXd was re-challenged following a grade 2 event, suggesting potential safety in select cases. While further studies are needed, pulmonologists and oncologists can consider rechallenging patients with severe pneumonitis who achieve complete symptomatic and radiographic resolution of pneumonitis after steroid treatment in those who were having good cancer control with T-DXd. This abstract is funded by: None