{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:03:40Z","timestamp":1793898220236,"version":"4.8.0"},"reference-count":26,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"Importance<\/jats:title>Non\u2013small cell lung cancer (NSCLC) with uncommon EGFR<\/jats:italic> mutations is a rare subgroup, composing 14% of all EGFR<\/jats:italic> mutations.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine the usefulness of osimertinib in previously untreated patients with metastatic NSCLC harboring uncommon EGFR<\/jats:italic> mutations, excluding exon 20 insertion mutations.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This multicenter, open-label, single-group, phase 2 nonrandomized clinical trial enrolled patients from April 10, 2020, to May 31, 2022, with a follow-up of 6 months from the date the last patient was enrolled. The study enrolled 42 patients with uncommon EGFR<\/jats:italic> mutations, of whom 40 were eligible.<\/jats:p><\/jats:sec>Intervention<\/jats:title>Osimertinib, 80 mg once daily, was administered orally to patients.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary end point was the overall response rate (ORR). The secondary end points were disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), duration of response (DoR), and safety of osimertinib. Patients were included in the study on an intention-to-treat basis.<\/jats:p><\/jats:sec>Results<\/jats:title>Of the 40 eligible patients, 22 were men (55.0%) and the median age was 72 years (range, 39.0-88.0 years). The most common mutations were G719X (20 [50.0%]), S768I (10 [25.0%]), and L861Q (8 [20.0%]). The ORR was 55.0% (90% CI, 40.9%-68.5%) and the DCR was 90.0% (95% CI, 76.3%-97.2%). The median PFS was 9.4 months (95% CI, 3.7-15.2 months) after a median follow-up of 12.7 months (range, 2.7-30.7 months). The median TTF was 9.5 months (95% CI, 5.6-30.3 months), median OS was not reached (NR; 95% CI, 19.3 months to NR), and median DoR was 22.7 months (95% CI, 9.5 months to NR). The ORR for patients with solitary or compound uncommon EGFR<\/jats:italic> mutations was 45.5% (90% CI, 26.9%-65.3%) and 66.7% (90% CI, 43.7%-83.7%), respectively. Median PFS for patients with solitary or compound uncommon EGFR<\/jats:italic> mutations was 5.4 months (95% CI, 3.6-22.7 months) and 9.8 months (95% CI, 5.1 months to NR), respectively. Median OS for patients with solitary or compound uncommon EGFR<\/jats:italic> mutations was 23.0 months (95% CI, 12.3 months to NR) and NR, respectively. Median DoR for patients with solitary or compound uncommon EGFR<\/jats:italic> mutations was 22.7 months (95% CI, 3.6-22.7 months) or NR (95% CI, 5.7 months to NR), respectively. Grade 3 or 4 adverse events were reported by 11 patients (27.5%), and 5 patients (12.5%) developed interstitial lung disease. All adverse events were manageable, and there were no treatment-related deaths.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>Osimertinib showed clinical activity with manageable toxic effects among previously untreated patients with metastatic NSCLC harboring uncommon EGFR<\/jats:italic> mutations other than exon 20 insertion mutations. 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