{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:21:50Z","timestamp":1790504510584,"version":"4.1.0"},"reference-count":30,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2019,8,1]]},"DOI":"10.1001\/jamaoncol.2019.1146","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T11:00:52Z","timestamp":1560423652000},"page":"1170","source":"Crossref","is-referenced-by-count":43,"title":["Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck"],"prefix":"10.1001","volume":"5","author":[{"given":"Barbara","family":"Burtness","sequence":"first","affiliation":[{"name":"Department of Medicine and Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Haddad","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Dinis","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas de Oncologia, Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Trigo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Virgen de la Victoria, IBIMA, Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Yokota","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Oncology, Shizuoka Cancer Centre, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"de Souza Viana","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Marcio Cunha, Ipatinga, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Romanov","sequence":"additional","affiliation":[{"name":"Russian Oncological Research Centre, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Vermorken","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Bourhis","sequence":"additional","affiliation":[{"name":"Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Tahara","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Medical Oncology, National Cancer Centre Hospital East, Kashiwa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Getulio","family":"Martins Segalla","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Hospital Amaral Carvalho, Jau, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Psyrri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Vasilevskaya","sequence":"additional","affiliation":[{"name":"Oncology Centre of Moskovskiy, St Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaitali Singh","family":"Nangia","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Centre, University of California at Irvine, Orange"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Chaves-Conde","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital Virgen del Rocio, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Kiyota","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Kobe University Hospital Cancer Center, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Homma","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Holeckova","sequence":"additional","affiliation":[{"name":"Department of Oncology and Radiotherapy, Hospital Na Bulovce and 1st Medical Faculty of Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep Maria","family":"Del Campo","sequence":"additional","affiliation":[{"name":"Department of Oncology, Vall d\u2019Hebron University Hospital, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirav","family":"Asarawala","sequence":"additional","affiliation":[{"name":"Shree Krishna Hospital and Medical Research Centre, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulisses Ribaldo","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, AC Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rauch","sequence":"additional","affiliation":[{"name":"Inselspital, University Hospital Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Even","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Cancer, Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushi","family":"Wang","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Gibson","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Ehrnrooth","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim, Danmark A\/S, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Harrington","sequence":"additional","affiliation":[{"name":"Division of Radiotherapy and Imaging, The Royal Marsden Hospital\/The Institute of Cancer Research, National Institute for Health Research Biomedical Research Centre, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezra E. W.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Translational Science, Moores Cancer Centre, University of California at San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the LUX-Head & Neck 2 investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"5","key":"coi190031r1","doi-asserted-by":"publisher","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int J Cancer"},{"issue":"3","key":"coi190031r2","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/ncponc0750","article-title":"The chemoradiation paradigm in head and neck cancer.","volume":"4","author":"Seiwert","year":"2007","journal-title":"Nat Clin Pract Oncol"},{"issue":"8","key":"coi190031r3","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1001\/jamaoncol.2016.5769","article-title":"Comparison of survival outcomes among human papillomavirus-negative cT1-2 N1-2b patients with oropharyngeal squamous cell cancer treated with upfront surgery vs definitive chemoradiation therapy: an observational study.","volume":"3","author":"Kelly","year":"2017","journal-title":"JAMA Oncol"},{"issue":"3","key":"coi190031r4","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/hed.v31:3","article-title":"Postradiotherapy neck dissection for head and neck squamous cell carcinoma: pattern of pathologic residual carcinoma and prognosis.","volume":"31","author":"Lango","year":"2009","journal-title":"Head Neck"},{"issue":"1","key":"coi190031r5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1056\/NEJMoa0912217","article-title":"Human papillomavirus and survival of patients with oropharyngeal cancer.","volume":"363","author":"Ang","year":"2010","journal-title":"N Engl J Med"},{"issue":"25","key":"coi190031r6","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1200\/JCO.2013.54.6309","article-title":"Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer.","volume":"32","author":"Cohen","year":"2014","journal-title":"J Clin Oncol"},{"issue":"3","key":"coi190031r7","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S1470-2045(13)70011-1","article-title":"Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial.","volume":"14","author":"Haddad","year":"2013","journal-title":"Lancet Oncol"},{"issue":"24","key":"coi190031r8","first-page":"7350","article-title":"Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma.","volume":"62","author":"Ang","year":"2002","journal-title":"Cancer Res"},{"issue":"6","key":"coi190031r9","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1056\/NEJMoa053422","article-title":"Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck.","volume":"354","author":"Bonner","year":"2006","journal-title":"N Engl J Med"},{"issue":"34","key":"coi190031r10","doi-asserted-by":"publisher","first-page":"8646","DOI":"10.1200\/JCO.2005.02.4646","article-title":"Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic\/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study.","volume":"23","author":"Burtness","year":"2005","journal-title":"J Clin Oncol"},{"issue":"11","key":"coi190031r11","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1056\/NEJMoa0802656","article-title":"Platinum-based chemotherapy plus cetuximab in head and neck cancer.","volume":"359","author":"Vermorken","year":"2008","journal-title":"N Engl J Med"},{"issue":"11","key":"coi190031r12","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1200\/JCO.2008.17.0530","article-title":"Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck","volume":"27","author":"Stewart","year":"2009","journal-title":"J Clin Oncol"},{"issue":"8","key":"coi190031r13","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1038\/bjc.2013.576","article-title":"ERCC1 is a prognostic biomarker in locally advanced head and neck cancer: results from a randomised, phase II trial.","volume":"109","author":"Bauman","year":"2013","journal-title":"Br J Cancer"},{"issue":"3","key":"coi190031r14","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1158\/1078-0432.CCR-16-0558","article-title":"HER3 targeting sensitizes HNSCC to cetuximab by reducing HER3 activity and HER2\/HER3 dimerization: evidence from cell line and patient-derived xenograft models.","volume":"23","author":"Wang","year":"2017","journal-title":"Clin Cancer Res"},{"issue":"5","key":"coi190031r15","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/S1470-2045(15)70124-5","article-title":"Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial.","volume":"16","author":"Machiels","year":"2015","journal-title":"Lancet Oncol"},{"issue":"36","key":"coi190031r16","doi-asserted-by":"publisher","first-page":"5294","DOI":"10.1200\/JCO.2010.30.6423","article-title":"Induction docetaxel, cisplatin, and cetuximab followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locally advanced head and neck cancer.","volume":"28","author":"Argiris","year":"2010","journal-title":"J Clin Oncol"},{"issue":"31","key":"coi190031r17","doi-asserted-by":"publisher","first-page":"4880","DOI":"10.1200\/JCO.2007.12.9650","article-title":"Phase I trial of gefitinib in combination with radiation or chemoradiation for patients with locally advanced squamous cell head and neck cancer.","volume":"25","author":"Chen","year":"2007","journal-title":"J Clin Oncol"},{"issue":"20","key":"coi190031r18","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.","volume":"310","author":"World Medical Association","year":"2013","journal-title":"JAMA"},{"issue":"35","key":"coi190031r21","doi-asserted-by":"publisher","first-page":"4202","DOI":"10.1200\/JCO.2015.61.4370","article-title":"Postoperative adjuvant lapatinib and concurrent chemoradiotherapy followed by maintenance lapatinib monotherapy in high-risk patients with resected squamous cell carcinoma of the head and neck: a phase III, randomized, double-blind, placebo-controlled study.","volume":"33","author":"Harrington","year":"2015","journal-title":"J Clin Oncol"},{"issue":"1","key":"coi190031r22","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1200\/JCO.1998.16.1.139","article-title":"Interpreting the significance of changes in health-related quality-of-life scores.","volume":"16","author":"Osoba","year":"1998","journal-title":"J Clin Oncol"},{"issue":"1","key":"coi190031r23","doi-asserted-by":"publisher","first-page":"67","DOI":"10.3892\/ijo.2014.2440","article-title":"A comprehensive evaluation of human papillomavirus positive status and p16INK4a overexpression as a prognostic biomarker in head and neck squamous cell carcinoma.","volume":"45","author":"Deng","year":"2014","journal-title":"Int J Oncol"},{"issue":"4","key":"coi190031r24","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1093\/annonc\/mdt574","article-title":"Impact of tumor HPV status on outcome in patients with recurrent and\/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial.","volume":"25","author":"Vermorken","year":"2014","journal-title":"Ann Oncol"},{"issue":"5","key":"coi190031r25","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1200\/JCO.2004.00.3335","article-title":"Molecular classification identifies a subset of human papillomavirus\u2013associated oropharyngeal cancers with favorable prognosis.","volume":"24","author":"Weinberger","year":"2006","journal-title":"J Clin Oncol"},{"issue":"10","key":"coi190031r26","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1093\/annonc\/mdx344","article-title":"Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and\/or metastatic head and neck cancer.","volume":"28","author":"Cohen","year":"2017","journal-title":"Ann Oncol"},{"issue":"2","key":"coi190031r27","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/S1470-2045(14)71198-2","article-title":"Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial.","volume":"16","author":"Mes\u00eda","year":"2015","journal-title":"Lancet Oncol"},{"issue":"43","key":"coi190031r28","doi-asserted-by":"publisher","first-page":"13225","DOI":"10.1073\/pnas.1518361112","article-title":"Inhibition of ErbB3 by a monoclonal antibody that locks the extracellular domain in an inactive configuration.","volume":"112","author":"Lee","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"coi190031r29","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41419-017-0029-0","article-title":"Anti-Trop2 blockade enhances the therapeutic efficacy of ErbB3 inhibition in head and neck squamous cell carcinoma.","volume":"9","author":"Redlich","year":"2018","journal-title":"Cell Death Dis"},{"issue":"15","key":"coi190031r30","doi-asserted-by":"publisher","first-page":"4331","DOI":"10.1158\/0008-5472.CAN-18-0459","article-title":"BET inhibition overcomes receptor tyrosine kinase-mediated cetuximab resistance in HNSCC.","volume":"78","author":"Leonard","year":"2018","journal-title":"Cancer Res"},{"key":"coi190031r19","volume-title":"The EORTC QLQ-C30 scoring manual","author":"Fayers","year":"2001","edition":"3rd ed"},{"key":"coi190031r20","unstructured":"Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE). National Cancer Institute. https:\/\/ctep.cancer.gov\/protocolDevelopment\/electronic_applications\/docs\/ctcaev3.pdf. Published August 9, 2006. Accessed May 15, 2019."}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/article-pdf\/5\/8\/1170\/17773660\/jamaoncology_burtness_2019_oi_190031.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T11:01:32Z","timestamp":1565262092000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2735890"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2019,8,1]]},"references-count":30,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2019.1146","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2019,8,1]]}}}