{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:00:23Z","timestamp":1790190023761,"version":"4.1.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019714","name":"Foundation Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019714","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Initial studies have shown improved outcomes in patients receiving cancer therapies matched to their molecular alterations. To improve the chances of finding a therapeutic match for patients, this study evaluated the preliminary antitumor activity of 3 commercially available multitargeted agents in the United States, regorafenib, afatinib, and cabozantinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this phase II trial, patients who did not benefit from first-line treatment for non-small cell lung cancer (NSCLC), upper aerodigestive tract cancers, non-colon gastrointestinal cancers, and urothelial carcinoma underwent next-generation sequencing to identify actionable genomic alterations. Eligible patients, based on identified mutations deemed treatable by regorafenib, cabozantinib, or afatinib, were enrolled to receive matched targeted therapies. Outcomes were monitored via Response Evaluation Criteria in Solid Tumors criteria, with dose modifications per National Cancer Institute Common Terminology Criteria for Adverse Events, v4.03 guidelines for adverse events (AEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>One hundred patients with metastatic cancers were enrolled across tumor types. Median treatment durations were 12\u2009weeks (regorafenib), 10.7\u2009weeks (afatinib), and 24.1\u2009weeks (cabozantinib). The overall objective response rate was 7.0%, with 1 complete response and 8 partial responses. The clinical benefit rate, including responses and stable disease &amp;gt;6\u2009months, was 16.0%. Median progression-free survival ranged from 1.9\u2009months for urothelial carcinoma to 3.2\u2009months for NSCLC. Toxicities were common for all medications; for regorafenib, 90.7% of patients had AEs (50% Grade 3\/4); for afatinib, 86% of patients had AEs (54% Grade 3\/4); for cabozantinib, 100% of patients had AEs (36% Grade 3\/4). The most common AEs were diarrhea, fatigue, nausea, decreased appetite, and stomatitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Regorafenib, afatinib, and cabozantinib had modest effects when used as molecularly matched targeted therapies in patients with NSCLC, upper aerodigestive tract cancers, non-colon gastrointestinal cancers, and urothelial carcinoma in the second-line setting. Future research could examine more precise matching of therapies to genomic alterations and evaluate combination therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag279","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:59:03Z","timestamp":1784721543000},"source":"Crossref","is-referenced-by-count":0,"title":["A phase II study to evaluate the efficacy of commercially available molecularly matched targeted therapies in the second-line setting"],"prefix":"10.1093","volume":"31","author":[{"given":"Suzanne","family":"Jones","sequence":"first","affiliation":[{"name":"Sarah Cannon Research Institute , Nashville, TN 37203,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Falchook","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute at HealthOne , Denver, CO 80218,","place":["United 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