Multicenter phase 2 trial of trastuzumab deruxtecan for HER2-expressing biliary tract cancer

Treatment options for patients with unresectable or recurrent biliary tract cancer (BTC) who progress on a gemcitabine-containing regimen are limited. About 5% to 30% of BTC patients have HER2-positive disease, and several HER2-targeted therapies have been reported to be effective for these patients. The phase 2 HERB trial, at 5 centers in Japan, evaluated trastuzumab deruxtecan (T-DXd) for HER2-expressing BTC in patients who were refractory or intolerant to a gemcitabine-containing regimen. Among patients with HER2-positive disease, the confirmed objective response rate was 36.4% (90% CI 19.6-56.1), meeting the primary end point. Among patients with HER2-low disease, the confirmed objective response rate was 12.5%. The most common grade 3 or greater adverse events were anemia (53.1%) and neutropenia (31.3%). 25% of patients had interstitial lung disease, including grade 5 events in 6% of patients. The authors conclude that T-DXd showed promising activity in patients with HER2-positive BTC and a signal of efficacy in patients with HER2-low BTC.