First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations – The UNICORN Phase 2 Nonrandomized Clinical Trial

Author(s): Yusuke Okuma, MD, PhD1; Kaoru Kubota, MD, PhD2; Mototsugu Shimokawa, PhD3; Kana Hashimoto, MD4; Yosuke Kawashima, MD5; Tomohiro Sakamoto, MD, PhD6; Hiroshi Wakui, MD, PhD7; Shuji Murakami, MD, PhD8; Kyoichi Okishio, MD, PhD9; Kenji Hayashihara, MD, PhD10; Yuichiro Ohe, MD, PhD1
Source: JAMA Oncol. 2024;10(1):43-51. doi:10.1001/jamaoncol.2023.5013
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

This study demonstrates activity of osimertinib in uncommon EGFR mutations. Of note, these were non-exon-20 mutations and included some with compound mutations. Response rates were reasonable and this justifies using targeted therapy in these uncommon subgroups.


Non–small cell lung cancer (NSCLC) with uncommon EGFR mutations is a rare subgroup, composing 14% of all EGFR mutations.


To determine the usefulness of osimertinib in previously untreated patients with metastatic NSCLC harboring uncommon EGFR mutations, excluding exon 20 insertion mutations.


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 mutations, of whom 40 were eligible.


Osimertinib, 80 mg once daily, was administered orally to patients.


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.


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 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 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 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 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.


Osimertinib showed clinical activity with manageable toxic effects among previously untreated patients with metastatic NSCLC harboring uncommon EGFR mutations other than exon 20 insertion mutations. The results support the use of osimertinib as a treatment option for this patient population.


Japan Registry of Clinical Trials Identifier: jRCTs071200002

Author Affiliations

1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; 2Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 3Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; 4Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan; 5Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan; 6Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Tottori, Japan; 7Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan; 8Division of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan; 9National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; 10National Hospital Organization Ibarakihigashi National Hospital, Tokai-mura, Naka-gun, Ibaraki, Japan

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