Actionable Genomic Alterations in Large Cell Neuroendocrine Carcinoma: A European Case Series of Patients Treated With a Small Molecule Inhibitor
Year: 2025
Type: article
Study design: Observational Study
Abstract: PURPOSE Actionable genomic alterations (AGA) are rare in large cell neuroendocrine carcinoma (LCNEC), and outcomes with small molecule inhibitors (SMI) are not well studied. We evaluated SMI response in LCNEC with AGAs, and also assessed molecular testing rates using the nationwide Netherlands Cancer Registry (NCR). MATERIALS AND METHODS In this European multicenter cohort, clinical data were collected from patients with LCNEC harboring AGAs (age 18 years and older) who were treated with an SMI. Overall survival (OS) was calculated from first-line systemic treatment to death or last follow-up. Radiologic response was evaluated for each treatment line. Molecular (AGA and retinoblastoma 1 gene [ RB1 ]) and immunohistochemical (protein RB1 [pRb] and Ki-67) data were collected. NCR data were analyzed to determine molecular testing frequency and AGA types in stage IV LCNEC (2016-2022). RESULTS In total, 28 patients with LCNEC were identified. The most common AGAs were epidermal growth factor receptor mutations (35.7%) and anaplastic lymphoma kinase fusions (32.1%). Median OS was 14.6 months (95% CI, 11 to 32). Across 38 SMI treatment lines, partial response was observed in 19 (50%). A trend toward longer survival was seen in patients with functional RB1 versus inactivated RB1 (hazard ratio, 0.32 [95% CI, 0.12 to 1.03]; P = .057). Within the NCR, molecular testing was conducted in 498/927 (53.7%) patients with stage IV LCNEC in the Netherlands, with AGAs detected in 111/498 (22.3%). CONCLUSION In our series, patients with LCNEC harboring AGAs who are treated with SMIs achieved a response in 50% of cases, including durable responses. However, only half of the patients with LCNEC are screened for AGAs. These findings highlight the need for standardized testing for AGAs in LCNEC.
Source: JCO Precision Oncology
DOI: 10.1200/po-25-00293
Authors: Frank W.J. Heijboer, Marta Brambilla, Mario Occhipinti, Daniele Lorenzini, Wieneke A. Buikhuisen, Liudmila L. Kodach, Petros Christopoulos, Albrecht Stenzinger, Lisa M. Hillen, Pilar Garrido, Yolanda Lage, Amparo Benito, Colin R. Lindsay, Mathew Carter, Judith Herder, Rieneke Britstra, Miep A. van der Drift, Wouter K. de Jong, Frans W.G. Schutgens, Ronald A.M. Damhuis, Ernst-Jan M. Speel, Jan H. von der Thüsen, Anne-Marie C. Dingemans, Jules L. Derks
Institutions: Erasmus MC, Erasmus MC Cancer Institute, Fondazione IRCCS Istituto Nazionale dei Tumori, The Netherlands Cancer Institute, Heidelberg University, University Hospital Heidelberg, Maastricht University Medical Centre, Maastricht University, Hospital Universitario Ramón y Cajal, University of Manchester, The Christie Hospital, The Christie NHS Foundation Trust, Meander Medisch Centrum, Radboud University Nijmegen, Radboud University Medical Center, University Medical Center Utrecht, Netherlands Comprehensive Cancer Organisation
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Pfizer
OpenAlex ID: W4416257015