Pooled analysis of trastuzumab deruxtecan for HER2-mutant metastatic non-small cell lung cancer with or without brain metastases

Brain metastases reduce overall survival rates of patients with non-small cell lung cancer; patients with HER2-mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved HER2-directed treatment for previously treated unresectable or metastatic HER2-mutant NSCLC. Pooled analysis of the multinational phase 2 DESTINY-Lung01 and DESTINY-Lung02 trials evaluated the effectiveness and safety of intravenous T-DXd 5.4 mg/kg and 6.4 mg/kg every 3 weeks for HER2-mutant metastatic NSCLC with or without treated or untreated stable brain metastases. The analysis included 243 particpants. Patients with and without brain metastases who received the T-DXd 5.4 mg/kg dose had systemic confirmed objective response rates of 47% and 50%, respectively, and an intracranial confirmed ORR of 50%. With the T-DXd 6.4 mg/kg dose, systemic confirmed ORRs were 50% and 59% for patients with and without brain metastases, respectively, and the intracranial confirmed ORR was 30%. The authors conclude that these findings support T-DXd use in patients with previously treated HER2-mutant metastatic NSCLC with or without brain metastases.