Steven B Maron1,2, Stephanie Moya3, Federica Morano4, Matthew J Emmett5, Joanne F Chou6, Shalom Sabwa1, Henry Walch6,7,8, Bryan Peterson3, Alexa B Schrock9, Liangliang Zhang9, Yelena Y Janjigian1,2, Sree Chalasani1, Geoffrey Y Ku1,2, Umut Disel10, Peter Enzinger11, Nataliya Uboha12, Shumei Kato13, Takayuki Yoshino14, Kohei Shitara14, Yoshiaki Nakamura14, Anwaar Saeed15, Pashtoon M Kasi16, Joseph Chao17, Jeeyun Lee18, Marinela Capanu6, Zev Wainberg19, Russell Petty20, Filippo Pietrantonio4, Samuel J Klempner5, Daniel V T Catenacci3. 1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. 2. Department of Medicine, Weill Cornell Medical College, New York, NY. 3. Department of Medicine, Division of Hematology-Oncology, University of Chicago School of Medicine, Chicago, IL. 4. Oncologia Medica, Instituto Nazionale dei Tumori di Milano, Milan, Italy. 5. Massachusetts General Hospital, Boston, MA. 6. Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. 7. Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY. 8. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY. 9. Foundation Medicine, Inc, Cambridge, MA. 10. Department of Medical Oncology, Adana Acibadem Hospital, Adana, Turkey. 11. Department of Medical Oncology, Dana-Farber Cancer Institute & Harvard Medical School, Boston, MA. 12. Department of Medicine, Section of Hematology & Oncology, Carbone Cancer Center, University of Wisconsin, Madison, WI. 13. Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA. 14. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 15. Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City, KS. 16. Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Medicine, University of Iowa, Iowa City, IA. 17. Department of Developmental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA. 18. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 19. Division of Oncology, Department of Medicine, UCLA School of Medicine, Los Angeles, CA. 20. Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom.
Abstract
PURPOSE: Subset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with EGFR-amplified GEA to date. PATIENTS AND METHODS: A total of 60 patients from 15 tertiary cancer centers in six countries met the inclusion criteria. These criteria required histologically confirmed GEA in the metastatic or unresectable setting with EGFR amplification identified by using a Clinical Laboratory Improvement Amendments-approved assay, and who received on- or off-protocol EGFRi. Testing could be by tissue next-generation sequencing, plasma circulating tumor DNA next-generation sequencing, and/or fluorescence in situ hybridization performed by a Clinical Laboratory Improvement Amendments approved laboratory. Treatment patterns and outcomes analysis was also performed using a deidentified clinicogenomic database (CGDB). RESULTS: Sixty patients with EGFR-amplified GEA received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median progression-free survival of 4.6 months (95% CI, 3.5 to 6.4). Patients receiving EGFRi in first-, second-, and third-line therapy achieved a median overall survival of 20.6 months (95% CI, 13.5 to not reached [NR]), 9 months (95% CI, 7.9 to NR), and 8.4 months (7.6 to NR), respectively. This survival far exceeded the 11.2-month (95% CI, 8.7 to 14.2) median overall survival from first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA in the CGDB. Despite this benefit, analysis of the CGDB (January 2011-December 2020) suggests that only 5% of patients with EGFR-amplified GEA received EGFRi. CONCLUSION: Patients with EGFR-amplified GEA derive significant benefit from EGFRi. Further prospective investigation of EGFRi in a well-selected patient population is ongoing in an upcoming trial of amivantamab in EGFR and/or MET amplified GEA.
PURPOSE: Subset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with EGFR-amplified GEA to date. PATIENTS AND METHODS: A total of 60 patients from 15 tertiary cancer centers in six countries met the inclusion criteria. These criteria required histologically confirmed GEA in the metastatic or unresectable setting with EGFR amplification identified by using a Clinical Laboratory Improvement Amendments-approved assay, and who received on- or off-protocol EGFRi. Testing could be by tissue next-generation sequencing, plasma circulating tumor DNA next-generation sequencing, and/or fluorescence in situ hybridization performed by a Clinical Laboratory Improvement Amendments approved laboratory. Treatment patterns and outcomes analysis was also performed using a deidentified clinicogenomic database (CGDB). RESULTS: Sixty patients with EGFR-amplified GEA received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median progression-free survival of 4.6 months (95% CI, 3.5 to 6.4). Patients receiving EGFRi in first-, second-, and third-line therapy achieved a median overall survival of 20.6 months (95% CI, 13.5 to not reached [NR]), 9 months (95% CI, 7.9 to NR), and 8.4 months (7.6 to NR), respectively. This survival far exceeded the 11.2-month (95% CI, 8.7 to 14.2) median overall survival from first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA in the CGDB. Despite this benefit, analysis of the CGDB (January 2011-December 2020) suggests that only 5% of patients with EGFR-amplified GEA received EGFRi. CONCLUSION: Patients with EGFR-amplified GEA derive significant benefit from EGFRi. Further prospective investigation of EGFRi in a well-selected patient population is ongoing in an upcoming trial of amivantamab in EGFR and/or MET amplified GEA.
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Authors: Xiuning Le; Sonam Puri; Marcelo V Negrao; Monique B Nilsson; Jacqulyne Robichaux; Theresa Boyle; J Kevin Hicks; Katherine L Lovinger; Emily Roarty; Waree Rinsurongkawong; Ming Tang; Huiying Sun; Yasir Elamin; Lara C Lacerda; Jeff Lewis; Jack A Roth; Stephen G Swisher; J Jack Lee; William N William; Bonnie S Glisson; Jianjun Zhang; Vassiliki A Papadimitrakopoulou; Jhanelle E Gray; John V Heymach Journal: Clin Cancer Res Date: 2018-09-18 Impact factor: 12.531
Authors: Kohei Shitara; Eric Van Cutsem; Yung-Jue Bang; Charles Fuchs; Lucjan Wyrwicz; Keun-Wook Lee; Iveta Kudaba; Marcelo Garrido; Hyun Cheol Chung; Jeeyun Lee; Hugo Raul Castro; Wasat Mansoor; Maria Ignez Braghiroli; Nina Karaseva; Christian Caglevic; Luis Villanueva; Eray Goekkurt; Hironaga Satake; Peter Enzinger; Maria Alsina; Al Benson; Joseph Chao; Andrew H Ko; Zev A Wainberg; Uma Kher; Sukrut Shah; S Peter Kang; Josep Tabernero Journal: JAMA Oncol Date: 2020-10-01 Impact factor: 31.777
Authors: Joseph Chao; Victoria Bedell; Jeeyun Lee; Min Sierra Li; Peiguo Chu; Yate-Ching Yuan; Dan Zhao; Samuel J Klempner; Ren-Jang Lin Journal: JAMA Netw Open Date: 2020-04-01