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The antibody-drug conjugate trastuzumab deruxtecan shrank tumours in about a third of Japanese patients with HER2-positive bile duct or gallbladder cancer after chemotherapy, and in one in eight with low HER2, but a quarter developed lung inflammation and two died of it.
Patients from five Japanese institutions with pathologically confirmed unresectable or recurrent biliary tract cancer, centrally confirmed HER2-positive (IHC 3+, or IHC 2+ and ISH-positive) or HER2-low (IHC 2+ and ISH-negative, IHC 1+, or IHC 0 and ISH-positive), refractory or intolerant to a gemcitabine-containing regimen, received trastuzumab deruxtecan 5.4 mg/kg every 3 weeks. The primary endpoint was confirmed objective response rate in HER2-positive disease by independent central review (threshold 15%, expected 40%).
32 patients were enrolled and treated. The 22 with HER2-positive disease had a confirmed objective response rate of 36.4% (90% CI 19.6 to 56.1; P = 0.01), meeting the primary endpoint; the 8 with HER2-low disease had a confirmed response rate of 12.5%. The most common grade 3 or worse treatment-related adverse events were anaemia (53.1%) and neutropenia (31.3%). Eight patients (25.0%) had interstitial lung disease, including two grade 5 events.
Together with the DESTINY-PanTumor02 biliary cohort this is the evidence behind trastuzumab deruxtecan's tumour-agnostic IHC 3+ label being used in gallbladder cancer; the lung toxicity rate, higher than in breast cancer, is the caution for a population with pre-existing lung and liver compromise.
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Biliary tract cancer (all types), HER2.
Shares National Cancer Center Hospital, Daiichi Sankyo, Trastuzumab deruxtecan.
Shares National Cancer Center Hospital, Biliary tract cancer (all types), HER2, Biliary tract cancer (cholangiocarcinoma).
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.