{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:32:10Z","timestamp":1792794730010,"version":"4.5.0"},"reference-count":29,"publisher":"American Medical Association (AMA)","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,5,13]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Treating locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) involves any combination of surgery, radiation, and chemotherapy, followed by routine monitoring for local recurrence or distant metastases. Given the poor patient outcomes, a significant unmet clinical need for improved treatment options remains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate efficacy and safety of maintenance atezolizumab in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>IMvoke010 was a phase 3, global, double-blind, randomized clinical trial. Patients were recruited at 128 sites in 23 countries between April 3, 2018, and February 14, 2020 (clinical cutoff date: September 27, 2023). Eligible patients had LA SCCHN (stage IVa\/IVb involving the oral cavity, larynx, hypopharynx, or human papillomavirus\u2013negative oropharynx, or stage III human papillomavirus\u2013positive oropharynx [<jats:italic>AJCC Cancer Staging Manual, <\/jats:italic>eighth edition]) without disease progression after multimodal definitive treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Patients were randomized (1:1) to receive atezolizumab 1200 mg or placebo every 3 weeks for 1 year or until disease recurrence, disease progression, unacceptable toxicity, or consent withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary end point was investigator-assessed event-free survival. Other end points included overall survival and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 406 patients were randomized to receive atezolizumab (n\u2009=\u2009203) or placebo (n\u2009=\u2009203); baseline demographics were balanced between both treatment groups (&amp;amp;lt;65 years, 142 [70.0%] vs 155 [76.4%]; male, 168 [82.8%] vs 174 [85.7%]; Asian, 68 [35.6%] vs 61 [31.0%]; Black, 1 [0.5%] vs 1 [0.5%]; and White, 121 [63.4%] vs 135 [68.5%], respectively). At clinical cutoff (median follow-up, 46.5 months), median investigator-assessed event-free survival was 59.5 months (95% CI, 46.8 to not estimable) with atezolizumab vs 52.7 months (95% CI, 41.4 to not estimable) with placebo (hazard ratio, 0.94; 95% CI, 0.70-1.26; <jats:italic>P<\/jats:italic>\u2009=\u2009.68). There was no difference in overall survival between atezolizumab and placebo (24-month overall survival, 82.0% vs 79.2%, respectively). No new or unexpected safety signals were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this study, atezolizumab did not improve clinical outcomes in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment. These data contribute to evidence on the limited activity of checkpoint inhibitors in the global population of this disease setting. Overall, the role of immunotherapy for patients with LA SCCHN remains to be determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03452137\">NCT03452137<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.2025.1483","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T15:01:27Z","timestamp":1741878087000},"page":"1599","source":"Crossref","is-referenced-by-count":63,"title":["Atezolizumab in High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck"],"prefix":"10.1001","volume":"333","author":[{"given":"Robert","family":"Haddad","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Fayette","sequence":"additional","affiliation":[{"name":"Centre Leon Berard, D\u00e9partement d\u2019H\u00e9matologie et d\u2019Oncologie, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Teixeira","sequence":"additional","affiliation":[{"name":"IPO de Coimbra, Servico de Oncologia Medica, Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar","family":"Prabhash","sequence":"additional","affiliation":[{"name":"Tata Memorial Hospital, Department of Medical Oncology, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricard","family":"Mesia","sequence":"additional","affiliation":[{"name":"Catalan Institute of Oncology, B-ARGO Group, IGTP, Badalona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Kawecki","sequence":"additional","affiliation":[{"name":"National Research Institute of Oncology, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunee","family":"Dechaphunkul","sequence":"additional","affiliation":[{"name":"Unit of Medical Oncology, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Dinis","sequence":"additional","affiliation":[{"name":"IPO do Porto, Servico de Oncologia Medica, Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai East Hospital, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneyuki","family":"Masuda","sequence":"additional","affiliation":[{"name":"National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Yun","family":"Hsieh","sequence":"additional","affiliation":[{"name":"China Medical University Hospital, Oncology and Hematology Office Critical Care Center, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Ghi","sequence":"additional","affiliation":[{"name":"Veneto Institute of Oncology, IRCCS, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Vaz de Melo Sette","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina do ABC\u2013FMABC, Santo Andr\u00e9, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Harrington","sequence":"additional","affiliation":[{"name":"The Royal Marsden Hospital\/The Institute of Cancer Research, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Tahara","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East, Kashiwa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil F.","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Lau","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibing","family":"Yan","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Ballinger","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Kaul","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Matheny","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaikunth","family":"Cuchelkar","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, University of California Los Angeles (UCLA)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"3","key":"joi250007r1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s40265-023-01835-2","article-title":"Treating head and neck cancer in the age of immunotherapy: a 2023 update.","volume":"83","author":"Bhatia","year":"2023","journal-title":"Drugs"},{"issue":"3","key":"joi250007r2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"joi250007r3","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma.","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat Rev Dis Primers"},{"issue":"7","key":"joi250007r4","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.3390\/v13071326","article-title":"A contemporary systematic review on repartition of HPV-positivity in oropharyngeal cancer worldwide.","volume":"13","author":"Carlander","year":"2021","journal-title":"Viruses"},{"issue":"9625","key":"joi250007r5","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1016\/S0140-6736(08)60728-X","article-title":"Head and neck cancer.","volume":"371","author":"Argiris","year":"2008","journal-title":"Lancet"},{"issue":"2","key":"joi250007r6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3390\/medsci11020042","article-title":"Epidemiology, risk factors, and prevention of head and neck squamous cell carcinoma.","volume":"11","author":"Barsouk","year":"2023","journal-title":"Med Sci"},{"issue":"3","key":"joi250007r7","doi-asserted-by":"publisher","first-page":"672","DOI":"10.3390\/cancers15030672","article-title":"Integrating immunotherapy into multimodal treatment of head and neck cancer.","volume":"15","author":"Rao","year":"2023","journal-title":"Cancers (Basel)"},{"issue":"11","key":"joi250007r9","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1016\/j.annonc.2020.07.011","article-title":"Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up.","volume":"31","author":"Machiels","year":"2020","journal-title":"Ann Oncol"},{"issue":"8","key":"joi250007r10","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1001\/jamaoncol.2019.1146","article-title":"Afatinib vs placebo as adjuvant therapy after chemoradiotherapy in squamous cell carcinoma of the head and neck: a randomized clinical trial.","volume":"5","author":"Burtness","year":"2019","journal-title":"JAMA Oncol"},{"issue":"2","key":"joi250007r11","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s40487-023-00226-7","article-title":"Induction therapy for locally advanced head and neck squamous cell carcinoma.","volume":"11","author":"Zheng","year":"2023","journal-title":"Oncol Ther"},{"issue":"10","key":"joi250007r12","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.3390\/cancers13102371","article-title":"Recurrent\/metastatic squamous cell carcinoma of the head and neck: a big and intriguing challenge which may be resolved by integrated treatments combining locoregional and systemic therapies.","volume":"13","author":"Ionna","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"29","key":"joi250007r13","doi-asserted-by":"publisher","first-page":"3293","DOI":"10.1200\/JCO.2015.61.1509","article-title":"Immunology and immunotherapy of head and neck cancer.","volume":"33","author":"Ferris","year":"2015","journal-title":"J Clin Oncol"},{"issue":"8","key":"joi250007r14","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1093\/annonc\/mdw217","article-title":"Immune escape to PD-L1\/PD-1 blockade: seven steps to success (or failure).","volume":"27","author":"Kim","year":"2016","journal-title":"Ann Oncol"},{"issue":"1","key":"joi250007r15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188386","article-title":"Priming the tumor immune microenvironment with chemo(radio)therapy: a systematic review across tumor types.","volume":"1874","author":"van den Ende","year":"2020","journal-title":"Biochim Biophys Acta Rev Cancer"},{"issue":"7528","key":"joi250007r19","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/nature14011","article-title":"Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.","volume":"515","author":"Herbst","year":"2014","journal-title":"Nature"},{"issue":"24","key":"joi250007r20","doi-asserted-by":"publisher","first-page":"6580","DOI":"10.1158\/1078-0432.CCR-12-1362","article-title":"Molecular pathways: next-generation immunotherapy\u2013inhibiting programmed death-ligand 1 and programmed death-1.","volume":"18","author":"Chen","year":"2012","journal-title":"Clin Cancer Res"},{"issue":"11","key":"joi250007r21","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1093\/annonc\/mdy411","article-title":"Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial.","volume":"29","author":"Colevas","year":"2018","journal-title":"Ann Oncol"},{"key":"joi250007r22","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy287.074","article-title":"IMvoke010: randomized phase III study of atezolizumab (atezo) as adjuvant monotherapy after definitive therapy of squamous cell carcinoma of the head and neck (SCCHN).","volume":"29","author":"Haddad","year":"2018","journal-title":"Ann Oncol"},{"issue":"1","key":"joi250007r23","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13000-023-01318-8","article-title":"Tumor Area Positivity (TAP) score of programmed death-ligand 1 (PD-L1): a novel visual estimation method for combined tumor cell and immune cell scoring.","volume":"18","author":"Liu","year":"2023","journal-title":"Diagn Pathol"},{"issue":"3","key":"joi250007r24","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1159\/000503095","article-title":"Performance status assessment by using ECOG (Eastern Cooperative Oncology Group) score for cancer patients by oncology healthcare professionals.","volume":"12","author":"Azam","year":"2019","journal-title":"Case Rep Oncol"},{"issue":"5","key":"joi250007r25","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/S1470-2045(24)00100-1","article-title":"Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial.","volume":"25","author":"Machiels","year":"2024","journal-title":"Lancet Oncol"},{"issue":"4","key":"joi250007r26","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1200\/JCO.21.02508","article-title":"Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: updated results of the phase III KEYNOTE-048 study.","volume":"41","author":"Harrington","year":"2023","journal-title":"J Clin Oncol"},{"issue":"4","key":"joi250007r27","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1093\/jjco\/hyaa268","article-title":"The role of radiotherapy in the age of immunotherapy.","volume":"51","author":"Sato","year":"2021","journal-title":"Jpn J Clin Oncol"},{"issue":"4","key":"joi250007r28","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/S1470-2045(20)30737-3","article-title":"Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.","volume":"22","author":"Lee","year":"2021","journal-title":"Lancet Oncol"},{"issue":"16","key":"joi250007r29","doi-asserted-by":"publisher","first-page":"6007","DOI":"10.1200\/JCO.2022.40.16_suppl.6007","article-title":"A randomized phase II study evaluating concurrent or sequential fixed-dose immune therapy in combination with cisplatin and intensity-modulated radiotherapy in intermediate- or high-risk, previously untreated, locally advanced head and neck cancer (LA SCCHN).","volume":"40","author":"Clump","year":"2022","journal-title":"J Clin Oncol"},{"key":"joi250007r8","unstructured":"National Comprehensive Cancer Network. National Comprehensive Cancer Network, head and neck cancers (version 2, 2025). Accessed August 5, 2024. https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/head-and-neck.pdf"},{"key":"joi250007r16","unstructured":"Food and Drug Administration. KEYTRUDA (pembrolizumab) highlights of prescribing information. Accessed August 5, 2024. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/125514s155lbl.pdf"},{"key":"joi250007r17","unstructured":"European Medicines Agency. Annex I: summary of product characteristics. Accessed August 5, 2024. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/opdivo-epar-product-information_en.pdf"},{"key":"joi250007r18","unstructured":"Food and Drug Administration. OPDIVO (nivolumab) highlights of prescribing information. Accessed August 5, 2024. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/125554s128lbl.pdf"}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/articlepdf\/2831624\/jama_haddad_2025_oi_250007_1746123761.73727.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:02:00Z","timestamp":1747148520000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2831624"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":29,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2025,5,13]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.2025.1483","relation":{},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5,13]]}}}