Pooled analysis by best confirmed response to trastuzumab deruxtecan and related biomarkers in patients with HER2-positive metastatic breast cancer

The DESTINY-Breast01/02/03 trials evaluated trastuzumab deruxtecan (T-DXd) in HER2-positive metastatic breast cancer (mBC). The objective response rates in the three trials were62%/70%/79%, respectively. Pooled analysis of the trials, investigating associations between best confirmed response to T-DXd and baseline characteristics/long-term outcome, has now been published. Among 834 patients, 125 experienced complete response (CR), 477 experienced partial response (PR), and 232 were non-responders (stable or progressive disease). Median number of prior regimes in the metastatic setting was 2 for patients with CR versus 3 for patients with PR or nonresponse. Visceral disease and baseline brain or bone metastases were less frequently observed in patients with CR, 24-month PFS rates in patients with CR, PR, and nonresponse, respectively, were 77.8%, 46.3%, and 20.6%, and 36-month OS rates were 88.6%, 54.0%, and 35.9%. Rates of serious adverse events, T-DXd discontinuation, and interstitial lung disease/pneumonitis were numerically lower in patients with CR. In exploratory biomarker analyses, responders had tumors with numerically higher HER2 plasma copy number, lower ESR1 gene expression and ESR1 mutation frequency, and lower circulating tumor DNA levels at baseline. The authors conclude that these results support T-DXd use across broad patient groups with HER2-positive mBC, including those with lower disease burden.