Trastuzumab Deruxtecan Shows Promise Among Patients With HER2-Expressing Unresectable or Recurrent Biliary Tract Cancer

According to results from a phase 2 study, trastuzumab deruxtecan demonstrated promising activity among patients with human epidermal growth factor receptor 2 (HER2)-expressing unresectable or recurrent biliary tract cancer. 

“Treatment options for patients with unresectable or recurrent biliary tract cancer who progress on a gemcitabine-containing regimen are limited,” stated Akihiro Ohba, MD, National Cancer Center Hospital, Tokyo, Japan, and coauthors. “In addition, the significance of anti–[HER2] therapy in HER2-expressing [biliary tract cancer] has not been sufficiently investigated.”

In this open-label, single-arm trial, researchers enrolled 32 patients with pathologically confirmed unresectable or recurrent biliary tract cancer with centrally confirmed HER2-positive (n = 22) or HER2-low (n = 8) disease who were refractory or intolerant to a gemcitabine-containing regimen. Patients received 5.4 mg/kg of trastuzumab deruxtecan once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was confirmed objective response rate (ORR) in the HER2-positive population. Secondary end points included confirmed ORR in the HER2-low population, disease control rate (DCR), median progression-free survival (PFS), overall survival (OS), and safety. 

At analysis, confirmed ORR was 36.4% in the HER2-positive population (90% confidence interval [CI], 19.6 to 56.1; P = .01) and median duration of response was 7.4 months. In the HER2-low population, confirmed ORR was 12.5%. The confirmed DCR was 81.8% in the HER2-positive population and 75% in the HER2-low population. The median PFS was 5.1 months in the HER2-positive population and 3.5 months in the HER2-low population, while the median OS was 7.1 months and 8.9 months, respectively. 

Grade ≥3 treatment-related adverse events were observed in 81.3% of patients, and most frequently included anemia (53.1%), neutropenia (31.3), decreased white blood cell count (31.3%), and decreased lymphocyte count (21.9%). It was noted that 4 patients developed grade ≥3 interstitial lung disease. Due to an adverse event, 25% of patients discontinued treatment in the HER2-positive population and 18.8% of patients discontinued treatment in the HER2-low population, while 2 treatment-related deaths occurred due to interstitial lung disease. Study authors recommend careful monitoring and early intervention for possible cases of interstitial lung disease. 

“[Trastuzumab deruxtecan] showed promising activity among patients with HER2-positive [biliary tract cancer] and signal of efficacy among patients with HER2-low [biliary tract cancer],” concluded Dr Ohba et al. 

“Antibody drug conjugates are proving to be a highly important therapeutic class of drugs,” added Journal of Clinical Oncology Associate Editor Eileen O’Reilly, MD, Memorial Sloan Kettering Cancer Center, New York, New York. “[Trastuzumab deruxtecan] is the first of its kind to demonstrate activity in biliary cancers and provides ongoing pathway validation for the importance of HER2 in these diseases.” 

Source: 

Ohba A, Kawamoto Y, Komatsu Y, et al. Trastuzumab deruxtecan in human epidermal growth factor receptor 2–expressing biliary tract cancer (HERB; NCCH1805): A multicenter, single-arm, phase II trial. J Clin Oncol. Published online: August 5, 2024. doi: 10.1200/JCO.23.02010