346MO - Trastuzumab deruxctecan (T-DXd) associated interstitial lung disease (ILD) in a large real-world French cohort of patients with HER2-driven breast cancer and other malignancies

Background

Trastuzumab Deruxtecan (T-DXd) presents a promising treatment for HER2-driven cancers but carries significant risks of interstitial lung disease (ILD).

Methods

We conducted a retrospective study of 600 patients (pts) from 11 French centers (April 2019-November 2023), analyzing clinical and radiological data for ILD with a centralized CT-scan review.

Results

Among 600 pts, the majority were female (95%), non-smokers (77%) with a median age of 60 years (IQR 55-73). 78% had prior chest radiotherapy, and 54% received prior HER2-targeted therapy. HER2-driven breast cancer prevailed (93%) with HER2-high in 54% and HER2-low in 39% and 3.8% had lung cancer. ILD occurred in 67 pts (11.2%) with a median onset of 82 days (IQR 49-192), often lacking respiratory symptoms (51%). Despite 55% with lung metastasis, 80% had controlled primary cancer at ILD onset. Radiological findings included ground glass opacities (87%) and consolidations (61%). Organizing pneumonia (OP) was the predominant pattern (52%) with atypical ovoid-shaped consolidations (25%)[jc1]. A diffuse alveolar damage (DAD) was seen in 9% of cases. ILD severity ranged mostly from grade 1-2 (81%) to grade 3-4 (10%), with fatal ILD in 9% (6/67), notably 4 with a DAD pattern. ILD onset occurred earlier in DAD pattern cases, with a median time of 51 days (IQR 40-55). Only 19 pts (all with an OP) had bronchoalveolar lavage which revealed a lymphocytic alveolitis (95%). T-DXd was withdrawn in 50 pts (75%), with 60% receiving corticosteroids, leading to improvement in 60%. Previous ILD was more frequently identified in pts who developed T-DXd-ILD (16/67) compared to those who did not (6/533, p<0.001).

Conclusions

Early detection and tailored management are crucial for T-DXd-induced ILD, given its potential severity despite controlled primary cancer. This study underscores specific radiological patterns among which DAD was usually fatal, emphasizing the importance of early treatment strategies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Canellas: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, Amgen. All other authors have declared no conflicts of interest.