Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study.
[en] [en] PURPOSE: To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) metastatic biliary tract cancer (mBTC).
METHODS: SGNTUC-019 (ClinicalTrials.gov identifier: NCT04579380) is an open-label phase II basket study evaluating the efficacy and safety of tucatinib and trastuzumab in patients with HER2-altered solid tumors. In the biliary tract cancer cohort, patients had previously treated HER2 overexpressing or amplified (HER2+) tumors (identified with local testing) with no prior HER2-directed therapy. The primary end point was confirmed objective response rate (cORR) per investigator assessment. Patients were treated on a 21-day cycle with tucatinib (300 mg orally twice daily) and trastuzumab (8 mg/kg intravenously followed by 6 mg/kg every 3 weeks).
RESULTS: Thirty patients were enrolled. As of data cutoff (January 30, 2023), the median duration of follow-up was 10.8 months. The cORR was 46.7% (90% CI, 30.8 to 63.0), with a disease control rate of 76.7% (90% CI, 60.6 to 88.5). The median duration of response and progression-free survival were 6.0 months (90% CI, 5.5 to 6.9) and 5.5 months (90% CI, 3.9 to 8.1), respectively. At data cutoff, 15 patients (50.0%) had died, and the estimated 12-month overall survival rate was 53.6% (90% CI, 36.8 to 67.8). The two most common treatment-emergent adverse events (TEAEs) were pyrexia (43.3%) and diarrhea (40.0%). Grade ≥3 TEAEs were reported in 18 patients (60.0%), with the most common being cholangitis, decreased appetite, and nausea (all 10.0%), which were generally not treatment related. TEAEs led to treatment regimen discontinuation in one patient, and there were no deaths due to TEAEs.
CONCLUSION: Tucatinib combined with trastuzumab had clinically significant antitumor activity and was well tolerated in patients with previously treated HER2+ mBTC.
Disciplines :
Oncology
Author, co-author :
Nakamura, Yoshiaki ; National Cancer Center Hospital East, Kashiwa, Japan
Mizuno, Nobumasa ; Aichi Cancer Center Hospital, Nagoya, Japan
Sunakawa, Yu ; St Marianna University Hospital, Kawasaki, Japan
Canon, Jean-Luc; Grand Hospital de Charleroi, Charleroi, Belgium
Galsky, Matthew D ; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
Hamilton, Erika ; Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN
Hayashi, Hidetoshi ; Kindai University Hospital, Osakasayama, Japan
Jerusalem, Guy ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Kim, Seung Tae ; Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea
Lee, Keun-Wook ; Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea
Kankeu Fonkoua, Lionel Aurelien; Mayo Clinic Rochester, Rochester, MN
Monk, Bradley J ; HonorHealth Research Institute, University of Arizona, Creighton University, Phoenix, AZ
Nguyen, Danny ; City of Hope National Medical Center, Duarte, CA
Oh, Do-Youn ; Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea
Okines, Alicia ; The Royal Marsden NHS Foundation Trust, London, UK
O'Malley, David M ; The Ohio State University & James Comprehensive Cancer Center, Columbus, OH
Pohlmann, Paula; MD Anderson Cancer Center, Houston, TX
Reck, Martin ; Department of Thoracic Oncology, Airway Research Center North, Germany Center for Lung Disease, Grosshansdorf, Germany
Shin, Sang Joon; Severance Hospital, Yonsei University Health System, Seoul, South Korea
Sudo, Kazuki ; National Cancer Center, Tokyo, Japan
Takahashi, Shunji ; Cancer Institute Hospital of JFCR, Tokyo, Japan
Van Marcke, Cedric ; Cliniques Universitaires Saint-Luc, Brussels, Belgium
Yu, Evan Y ; Fred Hutchinson Cancer Center/University of Washington, Seattle, WA
Groisberg, Roman ; Merck & Co, Inc, Rahway, NJ
Ramos, Jorge; Seagen Inc, Bothell, WA
Tan, Sherry; Seagen Inc, Bothell, WA
Stinchcombe, Thomas E ; Duke Cancer Institute, Durham, NC
Bekaii-Saab, Tanios ; Mayo Clinic Scottsdale, Scottsdale, AZ
Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study.
The authors thank the patients who participated in this trial, their families, and the investigators and staff at SGNTUC-019 clinical sites. Dr Nakamura thanks the SCRUM-Japan MONSTAR-SCREEN alliance for contributing to the patient recruitment at the Japanese study sites. The authors also thank Mark Bieda, PhD, Amanda Drees, PharmD, and Keith Earley, PhD, of Seagen Inc (Bothell, WA) for critical review of the data and the manuscript and Matthew Blahna, PhD, and Mariah van Waes, PharmD, of Seagen Inc for critical review of the manuscript. Finally, the authors thank the entire SGNTUC-019 study team for support. Kavya Kalachaveedu, PharmD, of MMS Holdings (Canton, MI) and Irene Park, PhD, of Seagen Inc provided medical writing and editorial support with funding from Seagen Inc, in accordance with Good Publication Practice guidelines. F. Hoffmann-La Roche, San Francisco, CA, provided trastuzumab for the study.
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