Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract or pancreatic tumors: a subgroup analysis of DESTINY-PanTumor02

BACKGROUND: In DESTINY-PanTumor02 Part 1, trastuzumab deruxtecan (T-DXd) demonstrated a clinically meaningful benefit in human epidermal growth factor receptor 2 (HER2)-expressing tumors. In this article, we report subgroup analyses in the biliary tract cancer (BTC) and pancreatic cancer (PC) cohorts from DESTINY-PanTumor02 Part 1. PATIENTS AND METHODS: DESTINY-PanTumor02 (NCT04482309) Part 1 evaluated T-DXd 5.4 mg/kg in locally advanced/metastatic HER2 immunohistochemistry (IHC) 3+/2+ (local/central testing) tumors that had progressed after systemic treatment or without treatment options. The primary endpoint was objective response rate (ORR) by investigator assessment (INV). Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory endpoints included outcomes by biomarker status and treatment history. RESULTS: Overall, 41 patients with BTC and 25 patients with PC had received T-DXd; median (range) follow-up duration was 6.01 (0.7-29.1) months and 4.99 (1.1-27.2) months, respectively. By INV, ORR was 22.0% [95% confidence interval (CI) 10.6%-37.6%] in the BTC cohort and 4.0% (95% CI 0.1%-20.4%) in the PC cohort; by independent central review, ORR was 26.8% (95% CI 14.2%-42.9%) and 12.0% (95% CI 2.5%-31.2%), respectively. Responses were seen across most patient subgroups in the BTC cohort; the highest ORR (56.3%, 95% CI 29.9%-80.2%) by INV was observed for those with HER2 IHC 3+ tumors (central test). Best objective response (by INV) of stable disease was observed in 61.0% of the BTC cohort and 68.0% of the PC cohort; median overall survival was 7.0 (95% CI 4.6-10.2) and 5.0 (95% CI 3.8-14.2) months, respectively. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 17.1% of patients with BTC and 4.0% of patients with PC. CONCLUSIONS: These data further support T-DXd as a recommended treatment in pretreated HER2 IHC 3+ tumors. Interpretation of PC cohort findings was limited by sample size and potentially confounded by the low number of patients with IHC 3+ PC. Safety was consistent with the known profile.