{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:27:19Z","timestamp":1790245639823,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>To the authors' knowledge, there are no approved therapies for recurrent, metastatic (R\/M) salivary gland carcinoma (SGC), but molecularly targeted therapies warrant ongoing investigation. In the current study, the authors have reported on the efficacy of tipifarnib in patients with aggressive <jats:italic>HRAS<\/jats:italic>\u2010mutant, R\/M SGC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The current prospective, nonrandomized, multicenter, international cohort study involved 8 centers and was conducted from May 2015 to June 2019. The median follow\u2010up was 22\u00a0months (range, 6\u201055\u00a0months). Subjects with <jats:italic>HRAS<\/jats:italic>\u2010mutant R\/M SGC (any histology) and disease progression within the last 6\u00a0months were enrolled. Tipifarnib was dosed orally twice daily. The authors determined the objective response rate using Response Evaluation Criteria in Solid Tumors (version 1.1), duration of response, and molecular predictors of response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 13 patients with R\/M SGC were enrolled; all had received prior systemic therapy (1\u20103 regimens). One objective response was observed; an additional 7 of 12 evaluable patients (58%) had stable disease as their best response with a median duration of 9\u00a0months (range, 3\u201014\u00a0months). Five of 7 patients had &gt;10% tumor regression and 6 of 7 had stable disease lasting &gt;6\u00a0months. Q61R was the most frequent activating <jats:italic>HRAS<\/jats:italic> mutation noted (7 of 13 patients; 54%), but gene variant and allele frequency did not correlate with outcomes. The median progression\u2010free survival was 7\u00a0months (95% confidence interval, 5.9\u201010.1\u00a0months), and the median overall survival was 18\u00a0months (95% confidence interval, 9.6\u201022.4\u00a0months) with approximately 58.6% of patients alive at 1\u00a0year. Survival was similar regardless of <jats:italic>HRAS<\/jats:italic> mutant variant or co\u2010occurring <jats:italic>PIK3CA<\/jats:italic> alterations. No participant discontinued treatment because of toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tipifarnib resulted in modest clinical activity with a promising disease control rate among patients with <jats:italic>HRAS<\/jats:italic>\u2010mutant, R\/M SGC who developed disease progression within the last 6\u00a0months.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33036","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:17:57Z","timestamp":1592479077000},"page":"3972-3981","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Tipifarnib in recurrent, metastatic HRAS\u2010mutant salivary gland cancer"],"prefix":"10.1002","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3870-8330","authenticated-orcid":false,"given":"Glenn J.","family":"Hanna","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Guenette","sequence":"additional","affiliation":[{"name":"Division of Neuroradiology Brigham &amp; Women's Hospital Dana\u2010Farber Cancer Institute Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole G.","family":"Chau","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology BC Cancer Vancouver Centre Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus M.","family":"Sayehli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II Early Clinical Trial Unit University Hospital Wurzburg Wurzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Plastic, Aesthetic and Reconstructive Head and Neck Surgery Julius Maximilian University of Wuerzburg Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Metcalf","sequence":"additional","affiliation":[{"name":"Medical Oncology The Christie NHS Foundation Trust Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Department of Medicine Ronald Reagan University of California at Los Angeles Medical Center Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Brose","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Hospital of the University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Razaq","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Stephenson Cancer Center The University of Oklahoma Oklahoma City Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-0800","authenticated-orcid":false,"given":"Elisabeth","family":"P\u00e9rez\u2010Ruiz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Institute of Biomedical Research of Malaga Costa del Sol Health Agency Marbella Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9872-6242","authenticated-orcid":false,"given":"Ezra E. W.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology Moores Cancer Center University of California at San Diego Health San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology University of California at San Francisco Helen Diller Family Comprehensive Cancer Center San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Scholz","sequence":"additional","affiliation":[{"name":"Kura Oncology San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gualberto","sequence":"additional","affiliation":[{"name":"Kura Oncology San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan L.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Memorial Sloan Kettering Cancer Center New York City New York"},{"name":"Department of Medicine Weill Cornell Medical College New York City New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2009.10.004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2016.2168"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70245-X"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0000000000000429"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2019.08.007"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-017-0833-y"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAT.0b013e3283484a60"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.25035"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx771"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(03)00097-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00545"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714448"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-2612"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx399"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4554"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.489"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.22.14459"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.TARG-19-PR08"},{"issue":"8","key":"e_1_2_8_20_1","first-page":"viii372","article-title":"Preliminary results from a phase 2 trial of tipifarnib in squamous cell carcinomas (SCCs) with HRAS mutations. ESMO 2018 Congress","volume":"29","author":"Ho AL","year":"2018","journal-title":"Ann Oncol"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2006.12.001"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.5076"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1925"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.8612"},{"key":"e_1_2_8_26_1","article-title":"Phase II trial of gefitinib in patients with incurable salivary gland cancer [abstract]","volume":"23","author":"Glisson B","year":"2005","journal-title":"Proc Am Soc Clin Oncol"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23647"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0637"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2643"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0231"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.6020"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.33036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.33036","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T13:55:09Z","timestamp":1760277309000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.33036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,18]]},"references-count":31,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1002\/cncr.33036"],"URL":"https:\/\/doi.org\/10.1002\/cncr.33036","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,18]]},"assertion":[{"value":"2020-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}