{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:11:10Z","timestamp":1792001470523,"version":"4.4.0"},"reference-count":11,"publisher":"Oxford University Press (OUP)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>On August 11, 2022, FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd, ENHERTU, Daiichi Sankyo) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The approval was based on a prespecified interim analysis of DESTINY-Lung02 (Study U206), a multi-center, randomized, dose-optimization trial in patients with NSCLC harboring activating HER2-mutations. At the approved dose of 5.4 mg\/kg given intravenously every 3 weeks, the overall response rate (ORR) was 58% (95% confidence interval [CI]: 43, 71). The median duration of response was 8.7 months (95% CI: 7.1, not estimable). These results were consistent with response rates observed at the 6.4 mg\/kg dose level. The most common (\u2265\u200520%) adverse reactions were nausea, constipation, decreased appetite, vomiting, fatigue, and alopecia. The rate of interstitial lung disease (ILD) or pneumonitis was 6% at the 5.4 mg\/kg dose level and 14% at the 6.4 mg\/kg dose level. In the setting of similar efficacy and reduced toxicity, approval was granted for the 5.4 mg\/kg dose level. The applicant conducted a randomized, dose-optimization study with guidance from the FDA Oncology Center of Excellence\u2019s Project Optimus. This is the first approval of a targeted therapy for HER2-mutated NSCLC.<\/jats:p>","DOI":"10.1093\/oncolo\/oyae151","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T12:15:04Z","timestamp":1720268104000},"page":"667-671","source":"Crossref","is-referenced-by-count":40,"title":["FDA approval summary: fam-trastuzumab deruxtecan-nxki for unresectable or metastatic non-small cell lung cancer with activating <i>HER2<\/i> mutations"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-6430","authenticated-orcid":false,"given":"Gautam U","family":"Mehta","sequence":"first","affiliation":[{"name":"Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, MD , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paz J","family":"Vellanki","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, U.S. Food and Drug Administration , 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