{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:25:05Z","timestamp":1789457105341,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"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":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Epidermal growth factor receptor (<jats:italic>EGFR<\/jats:italic>) exon 20 insertion (ex20ins) mutations are the third most common <jats:italic>EGFR<\/jats:italic> mutations in patients with non\u2013small cell lung cancer (NSCLC) and are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). There is evidence of activity of combining EGFR TKIs with monoclonal antibodies. This study reports on the efficacy and safety of afatinib in combination with cetuximab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this single\u2010arm phase 2 trial, patients with advanced NSCLC harboring an <jats:italic>EGFR<\/jats:italic> ex20ins mutation were treated with afatinib 40\u00a0mg once daily in combination with cetuximab 500\u00a0mg\/m<jats:sup>2<\/jats:sup> every 2 weeks. The primary end point was disease control rate (DCR) at 18\u00a0weeks of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010seven patients started treatment, with a median age of 65\u00a0years (range, 40\u201380\u00a0years), 78% female, and 95% White. The study achieved its primary end point with a DCR of 54% at 18\u00a0weeks, an overall response rate (ORR) of 43%, and a 32% confirmed ORR. Best responses were partial (<jats:italic>n<\/jats:italic>\u00a0=\u00a016), stable (<jats:italic>n<\/jats:italic>\u00a0=\u00a016), progressive disease (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), or not evaluable (<jats:italic>n<\/jats:italic>\u00a0=\u00a03). Median progression\u2010free survival was 5.5\u00a0months (95% CI, 3.7\u20138.3\u00a0months) and median overall survival was 16.8\u00a0months (95% CI, 10.7\u201325.8\u00a0months). The most common treatment\u2010related adverse events (TRAEs) were diarrhea (70%), rash (65%), dry skin (59%), paronychia (54%), and erythema (43%). Grade 3 TRAEs were reported in 54% of all patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Combination treatment with afatinib and cetuximab demonstrated antitumor activity with a DCR of 54% at 18\u00a0weeks and a 32% confirmed ORR. Toxicity was significant, although manageable, after dose reduction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35090","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T08:08:12Z","timestamp":1698739692000},"page":"683-691","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A phase 2 trial combining afatinib with cetuximab in patients with <i>EGFR<\/i> exon 20 insertion\u2013positive non\u2013small cell lung cancer"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3223-1255","authenticated-orcid":false,"given":"Bianca A. M. 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L.","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases Maastricht University Medical Center  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayed M. S.","family":"Hashemi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Amsterdam University Medical Centers, Vrije Universiteit Medical Center, and Cancer Center Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios","family":"Daletzakis","sequence":"additional","affiliation":[{"name":"Department of Biometrics Netherlands Cancer Institute\u2013Antoni van Leeuwenhoek Hospital  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan","family":"van den Broek","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Netherlands Cancer Institute\u2013Antoni van Leeuwenhoek Hospital  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda J. 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