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Trastuzumab Deruxtecan for HER2-Positive Biliary Cancer?
Biliary cancers frequently harbor targetable mutations and gene amplified pathways, including IDH-1, FGFR2, BRAF V600E, and human epidermal growth factor receptor 2 (HER2). There is increasing evidence that a range of HER2-targeted therapies are active in HER2-positive biliary cancer.
Investigators in Japan report the results of an industry-sponsored, single-arm, phase 2 trial of the antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in HER2-expressing advanced biliary cancer. Central pathologic confirmation of HER2 status by both immunohistochemistry and in situ hybridization was performed in archival tissue from 296 patients, of whom 61 (20.6%) tested HER2+. Thirty eligible patients were treated with T-DXd (5.4 mg/kg every 3 weeks), including 22 with HER2+ (IHC3+ or IHC2+/ISH+) and 8 with HER2 low (IHC 1–2+/ISH− or IHC−/ISH+) status. Most patients had gallbladder primary tumors (43.3%), followed by extrahepatic (26.7%) and intrahepatic (20.0%) biliary cancers; 70% had received two or more lines of prior therapy.
The primary endpoint of response rate in the 22 HER2+ patients was 36.4%. One of eight patients (12.5%) with HER2-low disease had a response. The median duration of response in the HER2+ patients was 7.4 months, and the median overall survival was 7.1 months. Two patients (6.0%) had fatal treatment-related interstitial lung disease.
Comment
Comment: The responses seen with T-DXd in HER2+ biliary cancers continue to validate that HER2 is targetable in biliary tract cancers; other active agents include trastuzumab/tucatinib and zanidatamab. Recently, T-DXd was granted accelerated approval by the U.S. FDA for use in patients with any advanced HER2+ solid tumors. Given the potential for use of targeted therapy in advanced biliary cancer, testing for biomarkers such as HER2 and performing next generation sequencing is now mandatory in these patients. In addition, careful monitoring for pulmonary toxicity to avoid potentially fatal drug-related interstitial lung disease is required.
Citation(s)
Author:
Ohba A et al.
Title:
Trastuzumab deruxtecan in human epidermal growth factor receptor 2-expressing biliary tract cancer (HERB; NCCH1805): A multicenter, single-arm, phase II trial.
Source:
J Clin Oncol
2024
Aug
5; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
David H. Ilson, MD, PhD