{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:04:41Z","timestamp":1789715081887,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>PD\u20101\/PD\u2010L1 inhibitors are standard therapy for advanced head and neck squamous cell carcinoma (HNSCC), but benefit only a subset of patients. Combining tyrosine kinase inhibitors (TKIs) with immunotherapy may improve outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following PRISMA 2020, PubMed, Embase, Cochrane Library and Web of Science were searched through January 2026 for clinical trials of PD\u20101\/PD\u2010L1 inhibitor monotherapy or TKI combination therapy in advanced HNSCC. Primary and secondary outcomes were objective response rate (ORR), 1\u2010year overall survival (OS), median OS, progression\u2010free survival (PFS) and safety. Random\u2010effects meta\u2010analyses, risk\u2010of\u2010bias assessment and GRADE evaluation were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven trials including 1190 patients were analysed. Combination therapy achieved a higher pooled ORR than monotherapy (36.2% vs. 16.6%; odds ratio 2.79, 95% CI 1.89\u20134.12;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The pooled 1\u2010year OS rate was also higher with combination therapy (63.8% vs. 37.8%). Median PFS ranged from 3.2 to 14.6\u2009months with combination therapy and 1.8\u20133.0\u2009months with monotherapy. Grade \u2265\u20093 adverse events, including hypertension, proteinuria and hand\u2010foot syndrome, were more frequent but manageable.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TKI plus PD\u20101\/PD\u2010L1 inhibition improves tumour response and may prolong survival, although evidence is limited by small early\u2010phase studies, heterogeneity and cross\u2010trial confounding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>PROSPERO CRD1297918.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70464","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:55:58Z","timestamp":1789714558000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of\n                    <scp>TKI<\/scp>\n                    Plus\n                    <scp>PD<\/scp>\n                    \u20101\/\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    Versus Monotherapy in Advanced\n                    <scp>HNSCC<\/scp>\n                    : A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6976-1040","authenticated-orcid":false,"given":"Zhengyan","family":"Luo","sequence":"first","affiliation":[{"name":"School of Stomatology Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyu","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Stomatology Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1854-2168","authenticated-orcid":false,"given":"Dongtao","family":"Wang","sequence":"additional","affiliation":[{"name":"Quanzhou Luojiang Weiming Stomatological Clinic  Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"issue":"12","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1158\/2159-8290.CD-13-0310","article-title":"Activation of the PD\u20101 Pathway Contributes to Immune Escape in EGFR\u2010Driven Lung Tumors","volume":"3","author":"Akbay E. 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