Real-world safety and effectiveness of trastuzumab deruxtecan (T-DXd) in HER2-overexpressing malignancies: A single-center retrospective study.

e15577 Background: HER2-overexpressing cancers represent a distinct group of malignancies. Based on the DESTINY-PanTumor02 trial, the FDA recently approved T-DXd for HER2-positive previously treated solid tumors. However, the trial excluded patients (pts) with an ECOG > 1 and those with brain metastases, leaving a gap in real-world data on the use of T-DXd in these frail populations. Methods: This single-center, IRB-approved, retrospective study included all pts with non-breast cancer who received at least one dose of T-DXd. The objective was to assess the real-world experience, particularly in pts who did not meet the clinical trial inclusion criteria. The primary objective was to assess safety, while secondary objectives included disease control rate (DCR, defined as partial response (PR) or stable disease (SD)), progression free survival (PFS), and overall survival (OS). Results: A total of 37 pts were included. Baseline characteristics are summarized in the table. Notably, 8 pts (22%) had ECOG > 1 and 9 (24%) had brain metastases. Adverse events (AEs) occurred in 30 pts (81%), leading to dose reductions (DR) in 15 pts (41%). Common AEs resulting in DR included fatigue (14%), cytopenia (8%), and anemia (5%). Nine pts (24%) had grade 3 or 4 AEs and 3 pts (8%) had grade 3 or 4 pneumonitis. The median final dose of T-DXd was 5.4 mg/kg (range: 3.2-6.4). Treatment discontinuation due to AEs was observed in 5 pts (13%), including pneumonitis (3 pts, 8%) and fatigue (2 pts, 5%). The median duration of treatment was 3.8 months (range: 0.5-21). The DCR was 69%, with 18 pts (49%) achieving PR and 7 (19%) achieving SD. Additionally, 7 pts (78%) with brain metastases achieved PR. In pts with HER2 3+ tumors, the DCR was 82%, with 5 pts (36%) achieving PR. Twelve pts (32%) received subsequent treatments, including chemotherapy (58%) and anti-HER2 therapies (42%), with a DCR of 50%. At the time of data cutoff, 16 pts (43%) remained on treatment. The median PFS was 7.3 months and the median OS was 10.2 months. Conclusions: T-DXd demonstrates a favorable safety profile and durable clinical benefit in a real-world, frailer pt population. The safety and efficacy data align with the results from the DESTINY-PanTumor02 trial, with pneumonitis observed in 8% of pts and a DCR of 69%. Further analysis of clinical and genomic risk factors will be presented. Baseline clinical characteristics. Median Age (range), yr 62 (29-82) Gender (male), n(%) 21(57) Race (white), n(%) 28(76) ECOG (>1), n(%) 8(22) Smoking history, n(%) 17(46) Primary cancer, n(%) Esophageal, 9(24); Colorectal, 7(19); Biliary tract, 5(14); Lung, 11(30); Gynecologic, 4(11) HER2 expression, n(%) Total, 20(54); HER2 2+, 6(16); HER2 3+, 14(38) ERBB2/HER2 amplification on FISH or NGS, n(%) 22(59) Comorbidity (COPD), n(%) 2(5) DCR by primary cancer type, n(%) Esophageal, 6(67); Colorectal, 4(57); Biliary tract, 4(80); Lung, 9(82); Gynecologic, 1(25)