{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:34:17Z","timestamp":1793385257069,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100001127","name":"Genentech Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001127","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp;amp; Neck"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Prognosis for patients with recurrent\/metastatic (R\/M) head and neck squamous cell cancer (HNSCC) remains poor. We hypothesized that the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to standard therapy would improve responses by inhibiting nuclear translocation of EGFR and designed a phase 2 trial of chemotherapy, cetuximab, and erlotinib in patients with R\/M HNSCC. A 24 patients were enrolled and treated with carboplatin, paclitaxel, and cetuximab administered in 21\u2010day\u2009cycles. Erlotinib was added with cycle 2. The primary end point was the objective response rate (ORR). The secondary end points were toxicity, overall survival (OS) and laboratory correlates. Median age was 65.5\u2009years. Median duration on treatment was 4.6\u2009months. ORR with cycle 1 of treatment was 33.3%, and for cycle 2 and beyond was 58.3%. Median progression\u2010free survival (PFS) was 6.2\u2009months, and median OS was 10.6\u2009months. Most common treatment\u2010related adverse events included anemia, neutropenia, skin rash, diarrhea, and hypomagnesemia. Dual EGFR blockade was tolerable and efficacious in this small patient sample. With an ORR of 58.3%, the study met its primary endpoint. PFS and OS were comparable to historical controls. Dual EGFR targeting without the chemotherapy backbone is worthy of further study.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trail Registration:<\/jats:bold>\n                    ClinicalTrials.gov identifier: NCT01316757.\n                  <\/jats:p>","DOI":"10.1002\/hed.28152","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T07:15:37Z","timestamp":1743578137000},"page":"2373-2382","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Phase\n                    <scp>II<\/scp>\n                    Trial of Chemotherapy, Cetuximab, and Erlotinib in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0491-4454","authenticated-orcid":false,"given":"Aarti","family":"Bhatia","sequence":"first","affiliation":[{"name":"Department of Internal Medicine (Oncology) Yale School of Medicine and Yale Cancer Center  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranee","family":"Mehra","sequence":"additional","affiliation":[{"name":"Director of Head and Neck Medical Oncology and Professor of Medicine Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8691-0387","authenticated-orcid":false,"given":"Jessica","family":"Bauman","sequence":"additional","affiliation":[{"name":"Division of Head and Neck Medical Oncology, Department of Hematology\/Oncology, Hematology\/Oncology Fellowship Training Program Fox Chase Cancer Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Associate Professor of Medicine (Oncology) Stanford University and Stanford Cancer Institute  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Internal Medicine (Oncology) Yale School of Public Health and Yale Cancer Center  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Neumeister","sequence":"additional","affiliation":[{"name":"Department of Pathology Associate Research Scientist in Pathology, Laboratory Director of the Specialized Translational Services Lab at Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Sandoval\u2010Schaefer","sequence":"additional","affiliation":[{"name":"Molecular, Cellular and Developmental Biology Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Katherine","family":"Alpaugh","sequence":"additional","affiliation":[{"name":"Protocol Support Laboratory Fox Chase Cancer Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Lango","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Division of Surgery The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Rimm","sequence":"additional","affiliation":[{"name":"Anthony N. Brady Professor of Pathology and Professor of Medicine (Medical Oncology) Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Ridge","sequence":"additional","affiliation":[{"name":"Louis Della Penna Family Chair in Head and Neck Oncology and Chief, Head and Neck Surgery Section Fox Chase Cancer Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Burtness","sequence":"additional","affiliation":[{"name":"Anthony N. Brady Professor of Medicine (Medical Oncology) Yale School of Medicine and Yale Cancer Center  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1715715"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32591-7"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000623"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00231-3"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2007.00510.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.03.003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.4.904"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.4646"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa053422"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802656"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012702"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-011-1128-4"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0370"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.19"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002442"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1993"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23499"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgq078"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2019.02.026"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2013.06.010"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0420"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000101047"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10194"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2825"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602999"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.06.075"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0562"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0870"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005933"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-008-0811-x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm791"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2018.06.032"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-28-113"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.30157"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01994"},{"key":"e_1_2_11_39_1","first-page":"CT012","volume-title":"Clinical Activity of MCLA\u2010158 (Petosemtamab), an IgG1 Bispecific Antibody Targeting EGFR and LGR5, in Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)","author":"Cohen E. E. W. F. J.","year":"2023"},{"key":"e_1_2_11_40_1","first-page":"6005","volume-title":"Dose Expansion Results of the Bifunctional EGFR\/TGF\u03b2 Inhibitor BCA101 With Pembrolizumab in Patients With Recurrent, Metastatic Head and Neck Squamous Cell Carcinoma","author":"Hanna G. J.","year":"2023"},{"key":"e_1_2_11_41_1","first-page":"5865","volume-title":"Isabelle Bergiers; Abstract 5865: Combinatorial Activity of Amivantamab and Pembrolizumab in Head and Neck Squamous Cell Carcinoma and Lung Squamous Cell Carcinoma Expressing Wild\u2010Type EGFR and MET","author":"Lim S. M.","year":"2023"}],"container-title":["Head &amp; Neck"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.28152","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hed.28152","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.28152","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:26:42Z","timestamp":1772983602000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hed.28152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":40,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/hed.28152"],"URL":"https:\/\/doi.org\/10.1002\/hed.28152","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.01.07.25320123","asserted-by":"object"}]},"ISSN":["1043-3074","1097-0347"],"issn-type":[{"value":"1043-3074","type":"print"},{"value":"1097-0347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]},"assertion":[{"value":"2025-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}