{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:15:20Z","timestamp":1783041320102,"version":"3.54.6"},"reference-count":41,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precision Oncology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> National Cancer Institute\u2013Molecular Analysis for Therapy Choice is a multicohort trial that assigns patients with advanced cancers to targeted therapies on the basis of central tumor genomic testing. Arm B evaluated afatinib, an ErbB family tyrosine kinase inhibitor, in patients with ERBB2-activating mutations. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> Eligible patients had selected ERBB2 single-nucleotide variants or insertions\/deletions detected by the National Cancer Institute\u2013Molecular Analysis for Therapy Choice next-generation sequencing assay. Patients had performance status \u2264 1, left ventricular ejection fraction &gt; 50%, grade \u2264 1 diarrhea, and no prior human epidermal growth factor receptor 2 (HER2) therapy. Patients received afatinib 40 mg once daily in 28-day cycles. The primary end point was objective response rate (ORR). Secondary end points were 6-month progression-free survival, overall survival, toxicity, and molecular correlates. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> A total of 59 patients were assigned and 40 were enrolled. The median age was 62 years, 78% were female, 68% had performance status = 1, and 58% had received &gt; 3 prior therapies. The confirmed ORR was 2.7% (n = 1 of 37; 90% CI, 0.14 to 12.2), and 6-month progression-free survival was 12.0% (90% CI, 5.6 to 25.8). A confirmed partial response occurred in a patient with adenocarcinoma of extra-mammary Paget disease of skin who progressed after cycle 6. Two unconfirmed partial responses were observed (low-grade serous gynecological tract and estrogen receptor\u2013positive\/HER2-negative immunohistochemistry breast ductal carcinoma). Of 12 patients with breast cancer, 1 additional patient with lobular carcinoma (estrogen receptor\u2013positive\/HER2 fluorescent in situ hybridization) had a 51% reduction in target lesions but progressed because of a new lesion at cycle 6. The most common (&gt; 20%) treatment-related adverse events were diarrhea (68%), mucositis (43%), fatigue (40%), acneiform rash (30%), dehydration (27%), vomiting (27%), nausea (27%), anemia (27%), and anorexia (22%). Four patients (11%) discontinued because of adverse events. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Although afatinib did not meet the prespecified threshold for antitumor activity in this heavily pretreated cohort, the response in a rare tumor type is notable. The safety profile of afatinib was consistent with prior studies. <\/jats:p><\/jats:sec>","DOI":"10.1200\/po.22.00165","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T19:59:36Z","timestamp":1659988776000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":19,"title":["Phase II Study of Afatinib in Patients With Tumors With Human Epidermal Growth Factor Receptor 2\u2013Activating Mutations: Results From the National Cancer Institute\u2013Molecular Analysis for Therapy Choice ECOG-ACRIN Trial (EAY131) Subprotocol EAY131-B"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6771-2999","authenticated-orcid":false,"given":"Philippe L.","family":"Bedard","sequence":"first","affiliation":[{"name":"Princess Margaret Cancer Centre, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuli","family":"Li","sequence":"additional","affiliation":[{"name":"E-A Biostatistical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3535-0652","authenticated-orcid":false,"given":"Kari B.","family":"Wisinski","sequence":"additional","affiliation":[{"name":"University of Wisconsin Carbone Cancer Center, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6450-2638","authenticated-orcid":false,"given":"Eddy S.","family":"Yang","sequence":"additional","affiliation":[{"name":"University of Alabama-Birmingham, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2170-5187","authenticated-orcid":false,"given":"Sewanti A.","family":"Limaye","sequence":"additional","affiliation":[{"name":"Kokilaben Dhirubhai Ambani Hospital, Mumbai, India (Current)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith P.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University Hospital, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-8789","authenticated-orcid":false,"given":"James A.","family":"Zwiebel","sequence":"additional","affiliation":[{"name":"Investigational Drug Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Moscow","sequence":"additional","affiliation":[{"name":"Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5724-4917","authenticated-orcid":false,"given":"Robert J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute\u2014ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Wang","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute\u2014ECOG-ACRIN Biostatistics Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8195-3206","authenticated-orcid":false,"given":"Lisa M.","family":"McShane","sequence":"additional","affiliation":[{"name":"Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-9737","authenticated-orcid":false,"given":"Larry V.","family":"Rubinstein","sequence":"additional","affiliation":[{"name":"Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3855-0166","authenticated-orcid":false,"given":"David R.","family":"Patton","sequence":"additional","affiliation":[{"name":"Center for Biomedical Informatics & Information Technology, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3309-5988","authenticated-orcid":false,"given":"P. 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