Trastuzumab deruxtecan rechallenge in HER2-positive metastatic breast cancer: EN-SEMBLE

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is a key treatment for HER2-positive metastatic breast cancer (mBC); however, data on T-DXd rechallenge remain limited. PATIENTS AND METHODS: This post-hoc subgroup analysis evaluated T-DXd rechallenge in patients with HER2-positive mBC using data from EN-SEMBLE, a nationwide cohort study in Japan (N = 664). RESULTS: Twenty-six patients were included. Median real-world progression-free survival, real-world time to treatment failure, and overall survival were 6.5, 4.9, and 14.2 months, respectively. The objective response rate was 27%. Patients who discontinued initial T-DXd without progressive disease had numerically longer real-world progression-free survival. No interstitial lung disease occurred during rechallenge. CONCLUSION: T-DXd rechallenge may have clinical activity in selected patients with HER2-positive mBC. CLINICAL TRIAL REGISTRATION NUMBER: jRCT1030220506.