Overexpression or amplification of HER2, which is present in 15% of all cases of bile duct cancer, has been identified as a molecular drug target by genomic profiling. In the Phase 3 ABC-06 trial, the folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen showed a survival advantage over active symptom control as a treatment for second line of cancer of the bile ducts. Our objective was to evaluate the clinical activity of FOLFOX plus trastuzumab, an anti-HER2 antibody, as a second- or third-line treatment for HER2-positive bile duct cancer.
34 participants were enrolled between June 26, 2020 and September 1, 2021. At the time of data cutoff on May 1, 2022, the median follow-up was 13 0 months (IQR 11 0–16 9), with three participants remaining on treatment. Ten patients had a partial response and 17 had stable disease; the overall response rate was 29.4% (95% CI 16.7–46.3) and the disease control rate was 79.4% (95% CI 62.9–89, 9). The median progression-free survival was 5.1 months (95% CI 3.6–6.7); median overall survival was 10·7 (95% CI 7·9–not achieved). The most common grade 3 or 4 treatment-related adverse events were neutropenia (ten
[29%] 3rd and 9th year participants [26%] grade 4), grade 3 anemia (five
[15%] participants), and grade 3 peripheral sensory neuropathy (four [12%] attendees). There were no cardiac toxic effects or treatment-related deaths. The global health assessment score (EuroQoL-VAS) did not change significantly throughout treatment. Symptoms of sensory and motor neuropathy, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Chemotherapy-Induced Peripheral Neuropathy Questionnaire, did not change from significantly over time.
For HER2-positive bile duct cancer, the second- or third-line biosimilar trastuzumab plus FOLFOX showed promising activity with acceptable toxicity, warranting further investigation.
Boryung Pharmaceutical, Celltrion, National Research Foundation of Korea, National R&D Program for Cancer Control through the National Cancer Center, Yonsei University College of Medicine.