{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:08:49Z","timestamp":1789556929920,"version":"build-2803163510"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Turning Point Therapeutics"},{"DOI":"10.13039\/100002491","name":"Bristol Myers Squibb Company","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"crossref"}]},{"name":"TRIDENT-1 ClinicalTrials.gov","award":["NCT03093116"],"award-info":[{"award-number":["NCT03093116"]}]},{"name":"National Cancer Institute\/National Institutes of Health","award":["P30CA008748"],"award-info":[{"award-number":["P30CA008748"]}]},{"name":"National Cancer Institute\/National Institutes of Health","award":["1R01CA226864"],"award-info":[{"award-number":["1R01CA226864"]}]},{"name":"Nonna\u2019s Garden"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Repotrectinib, a next-generation ROS1\/TRK tyrosine kinase inhibitor, is approved for ROS1 fusion-positive non-small cell lung cancer and NTRK fusion-positive solid tumors. Its side effects and safety management strategies require further characterization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>The safety profile of repotrectinib (treatment-emergent\/related adverse events [TEAEs\/TRAEs]) was established in patients who initiated treatment at the recommended dose (160\u2009mg daily [QD] for 14\u2009days, then 160\u2009mg twice daily [BID]) across all cohorts of the global, multicenter phase 1\/2 TRIDENT-1 study. AE management strategies were outlined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 472 patients, the most common TRAEs (dizziness [58%] and dysgeusia [50%]) were likely TRK inhibition-related. Median relative dose intensity was 90%; 14% (n\u2009=\u200966\/472) of patients did not increase their initial QD dose to BID (mostly due to CNS AEs). Rates of dizziness (median onset, 7\u2009days) were similar in patients with\/without baseline brain metastases. Dose modifications downgraded severity or resolved dizziness in 78% of patients; 58% of patients had pharmacologic intervention without dose modification. Dizziness was downgraded\/resolved in 62% (n\u2009=\u2009120\/195) of patients who did not receive dose modification or pharmacologic intervention. Treatment-related cognitive impairment and weight gain occurred in 19% and 12% of patients, respectively. Treatment-emergent withdrawal pain occurred in 14% of patients (median resolution time, 2.1\u2009weeks). Dose interruption and reduction from TRAEs occurred in 39% and 38% of patients, respectively; 10% reported later re-escalation back to 160\u2009mg BID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and\/or pharmacologic intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag137","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T11:28:48Z","timestamp":1776166128000},"source":"Crossref","is-referenced-by-count":1,"title":["Characterization and clinical management of adverse events following treatment with repotrectinib: a TRIDENT-1 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