ADC Therapy After Radiation: ILD Risk Assessment, Monitoring Intervals, and Rechallenge Strategies for Breast and Lung Cancer

This discussion brings together Dr. Hope Rugo, Dr. Aaron Lisberg, and Stephanie McDonald, NP discuss interstitial-lung-disease (ILD) risk assessment and monitoring strategies for patients receiving antibody-drug conjugates (ADCs) following radiation therapy.

Dr. Lisberg addresses whether prior radiation affects ADC use, emphasizing that recent radiation would not exclude patients from therapy given the efficacy of trastuzumab deruxtecan (T-DXd) in HER2-mutated non-small cell lung cancer and datopotamab deruxtecan in EGFR-mutant disease. He suggests considering a brief washout period if disease is not rapidly progressing, while acknowledging this must be individualized based on clinical urgency.

Regarding monitoring intervals, Dr. Lisberg reports scanning every 2 months initially, with 6-week intervals when clinical changes occur more rapidly. After approximately 6 months of stable therapy, scanning may extend to every 3 months. Dr. Rugo notes that pooled analysis data showed 89% of ILD cases occurred within the first 8 months, supporting more intensive early monitoring while maintaining vigilance for late events.

Dr. Rugo shares emerging data from a clinical trial combining radiation with T-DXd in HER2-positive breast cancer, reporting that radiation pneumonitis was distinguishable from drug-related ILD and rates remained low with minimal mortality.

McDonald emphasizes identifying high-risk patients, including those with prior thoracic radiation, previous chemotherapy, or severe lung disease, and coordinating with existing pulmonology relationships at baseline.

The panel concludes with consensus that ILD can present symptomatically or asymptomatically on imaging, and that early detection of grade 1 ILD enables steroid treatment, successful rechallenge, and continued benefit from effective therapy.