[en] Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated. SGNTUC-019 is an open-label, phase 2 basket study evaluating tucatinib, a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab in patients with HER2-altered solid tumors. The study included a cohort of 31 heavily pretreated female patients with HER2-mutated metastatic breast cancer who were also HER2 negative per local testing. Hormone receptor (HR)-positive patients also received fulvestrant. The overall response rate (primary endpoint) was 41.9% (90% confidence interval (CI): 26.9-58.2). Secondary endpoints of duration of response and progression-free survival were 12.6 months (90% CI: 4.7 to not estimable) and 9.5 months (90% CI: 5.4-13.8), respectively. No new safety signals were detected. Responses were observed across various HER2 mutations, including mutations in the tyrosine kinase and extracellular domains. The chemotherapy-free regimen of tucatinib and trastuzumab showed clinically meaningful antitumor activity with durable responses and favorable tolerability in heavily pretreated patients with HER2 mutations. These data support further investigation of HER2-targeted therapies in this patient population. ClinicalTrials.gov registration: NCT04579380 .
Disciplines :
Oncology
Author, co-author :
Okines, Alicia F C; The Royal Marsden NHS Foundation Trust, London, UK
Curigliano, Giuseppe ; Istituto Europeo di Oncologia, IRCCS, Milan, Italy ; University of Milano, Milan, Italy
Mizuno, Nobumasa ; Aichi Cancer Center Hospital, Nagoya, Japan
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
Rorive, Andrée ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Soliman, Hatem ; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Takahashi, Shunji; Cancer Institute Hospital of JFCR, Tokyo, Japan
Bekaii-Saab, Tanios ; Mayo Clinic, Scottsdale, AZ, USA
Burkard, Mark E; UW Carbone Cancer Center, University of Wisconsin, Madison, WI, USA
Chung, Ki Y; Prisma Health Institute, Greenville, SC, USA
Debruyne, Philip R ; Kortrijk Cancer Centre, General Hospital AZ Groeninge, Kortrijk, Belgium ; Medical Technology Research Centre (MTRC), School of Life Sciences, Anglia Ruskin University, Cambridge, UK ; School of Nursing and Midwifery, University of Plymouth, Plymouth, UK
Fox, Jenny R; Rocky Mountain Cancer Center, Boulder, CO, USA
Gambardella, Valentina; Hospital Clínico Universitario de Valencia, Valencia, Spain
Gil-Martin, Marta ; Institut Català d'Oncologia L'Hospitalet-IDIBELL, Hospitalet de Llobregat, Spain
Hamilton, Erika P ; Sarah Cannon Research Institute, Nashville, TN, USA
Monk, Bradley J; Florida Cancer Specialists and Research Institute, West Palm Beach, FL, USA
Nakamura, Yoshiaki ; National Cancer Center Hospital East, Kashiwa, Japan
Nguyen, Danny ; City of Hope National Medical Center, Duarte, CA, USA
O'Malley, David M; The Ohio State University and James Comprehensive Cancer Center, Columbus, OH, USA
Olawaiye, Alexander B; University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Pothuri, Bhavana; Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA
Reck, Martin; Department of Thoracic Oncology, Airway Research Center North, Germany Center for Lung Disease, Grosshansdorf, Germany
Sudo, Kazuki; National Cancer Center, Tokyo, Japan
Sunakawa, Yu ; St. Marianna University Hospital, Kawasaki, Japan
Van Marcke, Cedric; Cliniques Universitaires Saint-Luc, Brussels, Belgium
Yu, Evan Y; Fred Hutchinson Cancer Center/University of Washington, Seattle, WA, USA
Ramos, Jorge; Pfizer, Bothell, WA, USA
Tan, Sherry; Pfizer, Bothell, WA, USA
Bieda, Mark; Pfizer, Bothell, WA, USA
Stinchcombe, Thomas E ; Duke Cancer Institute, Durham, NC, USA
Pohlmann, Paula R ; University of Texas MD Anderson Cancer Center, Houston, TX, USA. prpohlmann@mdanderson.org
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