Rathi N Pillai1, Madhusmita Behera1, Lynne D Berry2, Mike R Rossi3, Mark G Kris4, Bruce E Johnson5, Paul A Bunn6, Suresh S Ramalingam1, Fadlo R Khuri1. 1. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia. 2. Vanderbilt Center for Quantitative Sciences, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee. 3. Division of Cancer Biology, Department of Radiation Oncology, Emory University, Atlanta, Georgia. 4. Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Clinical Research, Dana-Farber Cancer Institute, Boston, Massachusetts. 6. Division of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado.
Abstract
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC). METHODS: Patients with advanced-stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to examine 10 oncogenic drivers. The LCMC database was queried for patients with HER2 mutations to access demographic data, treatment history, and vital status. An exploratory analysis was performed to evaluate the survival of patients with HER2 mutations who were treated with HER2-directed therapies. RESULTS: A total of 920 patients were tested for HER2 mutations; 24 patients (3%) harbored exon 20 insertion mutations (95% confidence interval, 2%-4%). One patient had a concurrent mesenchymal-epithelial transition factor (MET) amplification. The median age of the patients was 62 years, with a slight predominance of females over males (14 females vs 10 males). The majority of the patients were never-smokers (71%) and presented with advanced disease at the time of diagnosis. The median survival for patients who received HER2-targeted therapies (12 patients) was 2.1 years compared with 1.4 years for those who did not (12 patients) (P = .48). Patients with HER2 mutations were found to have inferior survival compared with the rest of the LCMC cohort with other mutations: the median survival was 3.5 years in the LCMC population receiving targeted therapy and 2.4 years for patients not receiving targeted therapy. CONCLUSIONS: HER2 mutations were detected in 3% of patients with lung adenocarcinoma in the LCMC. HER2-directed therapies should be investigated in this subgroup of patients. Cancer 2017;123:4099-4105.
BACKGROUND:Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC). METHODS:Patients with advanced-stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to examine 10 oncogenic drivers. The LCMC database was queried for patients with HER2 mutations to access demographic data, treatment history, and vital status. An exploratory analysis was performed to evaluate the survival of patients with HER2 mutations who were treated with HER2-directed therapies. RESULTS: A total of 920 patients were tested for HER2 mutations; 24 patients (3%) harbored exon 20 insertion mutations (95% confidence interval, 2%-4%). One patient had a concurrent mesenchymal-epithelial transition factor (MET) amplification. The median age of the patients was 62 years, with a slight predominance of females over males (14 females vs 10 males). The majority of the patients were never-smokers (71%) and presented with advanced disease at the time of diagnosis. The median survival for patients who received HER2-targeted therapies (12 patients) was 2.1 years compared with 1.4 years for those who did not (12 patients) (P = .48). Patients with HER2 mutations were found to have inferior survival compared with the rest of the LCMC cohort with other mutations: the median survival was 3.5 years in the LCMC population receiving targeted therapy and 2.4 years for patients not receiving targeted therapy. CONCLUSIONS:HER2 mutations were detected in 3% of patients with lung adenocarcinoma in the LCMC. HER2-directed therapies should be investigated in this subgroup of patients. Cancer 2017;123:4099-4105.
Authors: D J Slamon; W Godolphin; L A Jones; J A Holt; S G Wong; D E Keith; W J Levin; S G Stuart; J Udove; A Ullrich Journal: Science Date: 1989-05-12 Impact factor: 47.728
Authors: Martine J Piccart-Gebhart; Marion Procter; Brian Leyland-Jones; Aron Goldhirsch; Michael Untch; Ian Smith; Luca Gianni; Jose Baselga; Richard Bell; Christian Jackisch; David Cameron; Mitch Dowsett; Carlos H Barrios; Günther Steger; Chiun-Shen Huang; Michael Andersson; Moshe Inbar; Mikhail Lichinitser; István Láng; Ulrike Nitz; Hiroji Iwata; Christoph Thomssen; Caroline Lohrisch; Thomas M Suter; Josef Rüschoff; Tamás Suto; Victoria Greatorex; Carol Ward; Carolyn Straehle; Eleanor McFadden; M Stella Dolci; Richard D Gelber Journal: N Engl J Med Date: 2005-10-20 Impact factor: 91.245
Authors: Alexa B Schrock; Garrett M Frampton; James Suh; Zachary R Chalmers; Mark Rosenzweig; Rachel L Erlich; Balazs Halmos; Jonathan Goldman; Patrick Forde; Kurt Leuenberger; Nir Peled; Gregory P Kalemkerian; Jeffrey S Ross; Philip J Stephens; Vincent A Miller; Siraj M Ali; Sai-Hong Ignatius Ou Journal: J Thorac Oncol Date: 2016-06-22 Impact factor: 15.609
Authors: Petra Heinmöller; Christof Gross; Kurt Beyser; Claudia Schmidtgen; Gerd Maass; Michele Pedrocchi; Josef Rüschoff Journal: Clin Cancer Res Date: 2003-11-01 Impact factor: 12.531
Authors: M G Kris; D R Camidge; G Giaccone; T Hida; B T Li; J O'Connell; I Taylor; H Zhang; M E Arcila; Z Goldberg; P A Jänne Journal: Ann Oncol Date: 2015-04-21 Impact factor: 32.976
Authors: Michael Offin; Daniel Feldman; Ai Ni; Mackenzie L Myers; W Victoria Lai; Elena Pentsova; Adrienne Boire; Mariza Daras; Emmet J Jordan; David B Solit; Maria E Arcila; David R Jones; James M Isbell; Kathryn Beal; Robert J Young; Charles M Rudin; Gregory J Riely; Alexander Drilon; Viviane Tabar; Lisa M DeAngelis; Helena A Yu; Mark G Kris; Bob T Li Journal: Cancer Date: 2019-08-30 Impact factor: 6.860
Authors: Tejas Patil; Rao Mushtaq; Sydney Marsh; Christine Azelby; Miheer Pujara; Kurtis D Davies; Dara L Aisner; William T Purcell; Erin L Schenk; Jose M Pacheco; Paul A Bunn; D Ross Camidge; Robert C Doebele Journal: Clin Lung Cancer Date: 2019-11-21 Impact factor: 4.785
Authors: Bob T Li; Ronglai Shen; Darren Buonocore; Zachary T Olah; Ai Ni; Michelle S Ginsberg; Gary A Ulaner; Michael Offin; Daniel Feldman; Todd Hembrough; Fabiola Cecchi; Sarit Schwartz; Nick Pavlakis; Stephen Clarke; Helen H Won; Edyta B Brzostowski; Gregory J Riely; David B Solit; David M Hyman; Alexander Drilon; Charles M Rudin; Michael F Berger; Jose Baselga; Maurizio Scaltriti; Maria E Arcila; Mark G Kris Journal: J Clin Oncol Date: 2018-07-10 Impact factor: 44.544
Authors: Bob T Li; Egbert F Smit; Yasushi Goto; Kazuhiko Nakagawa; Hibiki Udagawa; Julien Mazières; Misako Nagasaka; Lyudmila Bazhenova; Andreas N Saltos; Enriqueta Felip; Jose M Pacheco; Maurice Pérol; Luis Paz-Ares; Kapil Saxena; Ryota Shiga; Yingkai Cheng; Suddhasatta Acharyya; Patrik Vitazka; Javad Shahidi; David Planchard; Pasi A Jänne Journal: N Engl J Med Date: 2021-09-18 Impact factor: 176.079
Authors: Anna Michelotti; Marco de Scordilli; Elisa Bertoli; Elisa De Carlo; Alessandro Del Conte; Alessandra Bearz Journal: Int J Mol Sci Date: 2022-06-17 Impact factor: 6.208
Authors: W Victoria Lai; Louisiane Lebas; Tristan A Barnes; Julie Milia; Ai Ni; Oliver Gautschi; Solange Peters; Roberto Ferrara; Andrew J Plodkowski; John Kavanagh; Joshua K Sabari; Stephen J Clarke; Nick Pavlakis; Alexander Drilon; Charles M Rudin; Maria E Arcila; Natasha B Leighl; Frances A Shepherd; Mark G Kris; Julien Mazières; Bob T Li Journal: Eur J Cancer Date: 2019-01-24 Impact factor: 9.162