{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:03:06Z","timestamp":1790647386992,"version":"4.1.0"},"reference-count":30,"publisher":"Open Exploration Publishing","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Explor Target Antitumor Ther"],"accepted":{"date-parts":[[2026,8,7]]},"abstract":"<jats:p xml:lang=\"en\">Background: Preliminary findings from this study were previously published as a conference abstract (https:\/\/doi.org\/10.1158\/2326-6074.IO2025-B039). Immune checkpoint inhibitors (ICIs) have shown activity in nasopharyngeal carcinoma (NPC), but their efficacy and safety when integrated with standard chemoradiotherapy (CRT) for locally advanced NPC remain under investigation. We performed a systematic review and meta-analysis of randomized controlled trials evaluating the efficacy and safety of integrating ICIs with standard CRT-based treatment in patients with locally advanced NPC. Methods: MEDLINE and EMBASE were searched from inception through September 1, 2025, for English-language phase II or III randomized controlled trials evaluating ICIs plus standard therapy. Eligible studies reported efficacy outcomes, including progression-free\/event-free survival (PFS\/EFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS), and\/or safety outcomes. Hazard ratios (HRs) were pooled using the generic inverse variance method, and risk ratios (RRs) for adverse events were pooled using the Mantel-Haenszel method. Fixed-effect models were used, with heterogeneity assessed using I2 statistics. Results: Three trials randomized 1,022 patients: CONTINUUM (n = 423), DIPPER (n = 450), and a phase II toripalimab trial (n = 149). The pooled safety population included 998 patients. ICIs significantly improved PFS\/EFS [HR 0.54; 95% confidence interval (CI): 0.40\u20130.72; P &lt; 0.0001], DMFS (HR 0.52; 95% CI: 0.36\u20130.75; P = 0.0005), and LRFS (HR 0.47; 95% CI: 0.31\u20130.71; P = 0.0003). OS favored the ICI arm but was not statistically significant (HR 0.77; 95% CI: 0.49\u20131.20; P = 0.24). ICIs increased immune related adverse events, whereas most CRT-associated locoregional and hematologic toxicities were not significantly increased. Discussion: Adding ICIs to standard CRT based therapy significantly improved disease control outcomes, including PFS\/EFS, DMFS, and LRFS, without broadly worsening the overall CRT associated toxicity profile. Longer follow up is needed to determine whether these early disease control benefits translate into a statistically significant OS advantage.<\/jats:p>","DOI":"10.37349\/etat.2026.1002403","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:43:21Z","timestamp":1790646201000},"update-policy":"https:\/\/doi.org\/10.37349\/open_exploration_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Addition of immune checkpoint inhibitor to standard of care chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma: a systematic review and meta-analysis"],"prefix":"10.37349","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5776-0222","authenticated-orcid":false,"given":"Ramaditya","family":"Srinivasmurthy","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Mount Sinai Morningside, New York, NY 10019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8514-2781","authenticated-orcid":false,"given":"Jason","family":"Ta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, HCA Healthcare, HCA Florida Citrus Hospital, Inverness, FL 34452, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharif","family":"Afifi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV 89154, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2034-3283","authenticated-orcid":false,"given":"Taimur","family":"Khalid","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV 89154, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3085-1549","authenticated-orcid":false,"given":"Hazem","family":"Aboaid","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV 89154, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishi Kumar","family":"Nanda","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine, Touro University Nevada, Henderson, NV 89014, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Thomas","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Sunrise Health GME Consortium, HCA Healthcare, Las Vegas, NV 89128, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV 89154, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Nguyen","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine, Touro University Nevada, Henderson, NV 89014, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Fama","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine, Touro University Nevada, Henderson, NV 89014, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Aamer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV 89154, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin Mon","family":"Myat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Interfaith Medical Center Campus, One Brooklyn Health, Brooklyn, NY 11213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo-Lawrence","family":"Bigcas","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV 89154, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1518-1097","authenticated-orcid":false,"given":"Kyaw Zin","family":"Thein","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV 89169, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"21850","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1158\/1055-9965.epi-20-1702","article-title":"The Evolving Epidemiology of Nasopharyngeal Carcinoma","volume":"30","author":"Chang","year":"2021","journal-title":"Cancer Epidemiol Biomark 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Available from: https:\/\/www.cancer.org\/cancer\/types\/nasopharyngeal-cancer\/treating\/immunotherapy.html"},{"key":"ref7","unstructured":"American Cancer Society. Immune checkpoint inhibitors and their side effects [Internet]. American Cancer Society; c2026 [cited 2025 Jan 20]. Available from: https:\/\/www.cancer.org\/cancer\/managing-cancer\/treatment-types\/immunotherapy\/immune-checkpoint-inhibitors.html"},{"key":"ref8","unstructured":"Mayo Clinic. Immune checkpoint inhibitors and thyroid dysfunction: a case from the endocrine teaching clinics [Internet]. Mayo Foundation for Medical Education and Research (MFMER); c1998-2026 [cited 2025 Feb 01]. 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