Balancing Safety and Efficacy With ADC-Based Therapies in Advanced EGFRm Non–Small Cell Lung Cancer

This video segment focuses on the safety and efficacy profile of antibody-drug conjugates (ADCs) in advanced EGFR-mutated non–small cell lung cancer, particularly comparing datopotamab deruxtecan (dato-DXd) and patritumab deruxtecan. Dato-DXd demonstrates superior efficacy compared with traditional chemotherapy options like docetaxel, with response rates around 30% and better progression-free survival outcomes. The agent has received FDA approval for breast cancer and is being used off-label in heavily pretreated patients with lung cancer as an alternative to conventional single-agent chemotherapies like docetaxel, gemcitabine, or irinotecan.

The discussion highlights distinct toxicity profiles between different ADCs that clinicians must consider when selecting treatments. Patritumab deruxtecan presents adverse effects similar to conventional chemotherapy, including significant nausea requiring proactive antiemetic protocols and myelosuppression, but is generally manageable with standard supportive care measures. Dato-DXd has unique toxicities including stomatitis (mouth sores) that can be challenging for patients, requiring prophylactic interventions like dexamethasone rinses and ice chip therapy during treatment, as well as potential ocular toxicities that need monitoring.

A critical safety concern across all ADCs is the risk of interstitial lung disease (ILD), though fortunately the incidence appears lower than seen with other ADCs like trastuzumab deruxtecan in HER2-mutated populations. However, ILD monitoring protocols for ADCs differ from immunotherapy approaches, requiring more cautious management with treatment interruption recommended even for grade 1 ILD findings. Patients with a history of ILD would require very careful risk-benefit discussions before considering ADC therapy. Without reliable biomarkers for patient selection, treatment decisions often come down to individualized discussions about toxicity tolerance and patient preferences regarding different adverse effect profiles.