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Войти в исследования Journal of the National Cancer Institute · 2026
NRG1 fusion-positive solid tumors: clinical detection, genomic landscape, and real-world data in pancreatic cancer.
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Schram Alison M, Yang Soo-Ryum, Kahn Genessa, Velasco Rogelio, Repetto Matteo, Kinh Gian Do Richard, DiNapoli Sara, Sukhadia Purvil, Troxel Megan, Ozcan Kerem, Tarcan Zeynep, Ladanyi Marc, Harding James J, Drilon Alexander, Basturk Olca, O'Reilly Eileen M
Аннотация
BACKGROUND: NRG1 fusions are unique oncogenic drivers that activate the HER3/HER2/PI3K pathway. The US Food and Drug Administration granted accelerated approval to a HER2/HER3 antibody, zenocutuzumab, for treatment of NRG1 fusion-positive non-small cell lung cancer and pancreatic ductal adenocarcinoma (PDAC). The optimal detection methods and clinicopathological features of patients with NRG1 fusion-positive cancer have not been systematically studied. Here, we review NRG1 fusion-positive cancer and focus on outcomes in PDAC.
METHODS: Patients with NRG1 fusion-positive disease at Memorial Sloan Kettering Cancer Center were identified using institutional databases. Clinicopathological data were extracted from medical records. NRG1 fusion-positive PDAC cases underwent review of radiology, pathology, treatment data, and assessment of progression-free and overall survival.
RESULTS: Of 76 531 patients, 48 NRG1 fusion-positive cases were identified. The most common tumor types were lung (60%), PDAC (21%), and breast (10%). Approximately half (46%) of these patients received HER2- and/or HER3-directed therapy. Patients were identified by RNA (n = 34), DNA (n = 11), or both (n = 3). RNA was superior to DNA for fusion identification. Twenty-one fusion partners were detected, most commonly CD74 (40%) and ATP1B1 (10%). Lung cancers were otherwise driver negative, and PDAC cases were KRAS wild type. NRG1 fusion-positive PDAC exhibited distinct histopathological and clinical features. Median patient age was 48.5 years, median progression-free survival on first-line chemotherapy was 12.6 months (n = 7; 95% confidence interval [CI] = 2.9 to not reached), and median overall survival from diagnosis was 39.6 months (n = 9; 95% CI = 23.2 to not reached).
CONCLUSIONS: NRG1 fusions are a newly described, clinically actionable target in solid tumors. We report the landscape of NRG1 fusion-positive cancers and highlight the importance of RNA testing. NRG1 fusion-positive PDAC is enriched in younger patients with KRAS wild-type disease and has unique biology.
METHODS: Patients with NRG1 fusion-positive disease at Memorial Sloan Kettering Cancer Center were identified using institutional databases. Clinicopathological data were extracted from medical records. NRG1 fusion-positive PDAC cases underwent review of radiology, pathology, treatment data, and assessment of progression-free and overall survival.
RESULTS: Of 76 531 patients, 48 NRG1 fusion-positive cases were identified. The most common tumor types were lung (60%), PDAC (21%), and breast (10%). Approximately half (46%) of these patients received HER2- and/or HER3-directed therapy. Patients were identified by RNA (n = 34), DNA (n = 11), or both (n = 3). RNA was superior to DNA for fusion identification. Twenty-one fusion partners were detected, most commonly CD74 (40%) and ATP1B1 (10%). Lung cancers were otherwise driver negative, and PDAC cases were KRAS wild type. NRG1 fusion-positive PDAC exhibited distinct histopathological and clinical features. Median patient age was 48.5 years, median progression-free survival on first-line chemotherapy was 12.6 months (n = 7; 95% confidence interval [CI] = 2.9 to not reached), and median overall survival from diagnosis was 39.6 months (n = 9; 95% CI = 23.2 to not reached).
CONCLUSIONS: NRG1 fusions are a newly described, clinically actionable target in solid tumors. We report the landscape of NRG1 fusion-positive cancers and highlight the importance of RNA testing. NRG1 fusion-positive PDAC is enriched in younger patients with KRAS wild-type disease and has unique biology.