Trastuzumab deruxtecan in human epidermal growth factor receptor 2-expressing biliary tract cancer (HERB; NCCH1805): a multicenter, single-arm, phase II trial
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.
Overview
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.
- Confirmed objective response rate 36.4% (8 of 22) in HER2-positive and 12.5% (1 of 8) in HER2-low biliary tract cancer.
- Grade 3 or worse anaemia 53.1% and neutropenia 31.3%.
- Interstitial lung disease in 25.0% (8 of 32), two fatal.
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.
- 32 patients, single arm, Japanese centres only.
- Two treatment-related deaths from interstitial lung disease in a small cohort.
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