Clinical Outcomes for Patients who Received Both Trastuzumab Deruxtecan (T-DXd) and Trastuzumab Emtansine (T-DM1) for HER2-Mutant non-Small Cell Lung Cancer

Whether patients benefit from sequential HER2-directed ADCs therapy remains unknown. Clinical characteristics, confirmed overall response rate, real-world progression-free survival (rwPFS), and overall survival (OS) were evaluated. All time-to-event endpoints were calculated from the start of the second ADC. Results: kinase-domain mutations, while 3 had extracellular and 1 had transmembrane domain alterations. The median number of prior systemic therapies before the second ADC was three. Seventeen patients (68%) received the two ADCs in direct sequence without other intervening therapies. In the T-DM1 post-T-DXd cohort, the median rwPFS was 3.3 months (95% CI, 1.9-5.6) and the median OS was 9.2 months (95% CI, 4.9-NR). No confirmed responses were observed; however, two patients (12%) achieved unconfirmed partial responses, and one had prolonged stable disease for 13.9 months. In the T-DXd post-T-DM1 cohort, the median rwPFS was 5.2 months (95% CI, 4.1-NR) and the median OS was 25.0 months (95% CI, 8.2-NR); three patients (37.5%) achieved confirmed partial responses. Understanding the mechanisms of response and resistance to ADCs will hopefully help to inform treatment strategies using sequential ADCs in lung cancer and other malignancies.