Abstract CT164: Efficacy and safety of osimertinib therapy in high-risk stage I EGFRm NSCLC after R0 resection(OSTAR): A phase II, prospective, single-arm study

Abstract Background: For patients with stage I non-small cell lung cancer who have been completely resected, pathology confirmed solid and/or micropapillary components≥10%, and/or complex glands ≥15%, and/or spread through air space(STAS) are more likely to relapse and meanwhile have no or limited benefit from adjuvant chemotherapy. The study ADAURA indicated that Osimertinib significantly decreased a 59% risk of recurrence or death in the stage IB subgroup (HR=0.41,95% CI:0.23-0.69). Whether these NSCLC patients with stage I complicated with the above high-risk factors would benefit from adjuvant therapy with osimertinib is unknown. Methods: This single center, phase II study enrolled 70 patients (pts) between October, 2022 and June, 2024. These EGFR-sensitive mutation patients through complete resection and diagnosed as stage I NSCLC(AJCC8th ) with high-risk factors received adjuvant osimertinib (80mg QD) for 3 years. The data cut-off (DCO) was October 29, 2024. The primary endpoint is the 3-year DFS rate. Results: Median follow-up and duration of total treatment exposure time were 14 months and 14.1 months (range, 3 to 24), respectively. Baseline characteristics are shown in Table 1 Table 1 Baseline characteristics Osimertinib 80mg qd N=70 Age, median(range) , yr 60 (39,76) Sex, n(%) Female 47 (67.14) Male 23 (32.86) Stage, n(%) IA1 3 (4.29) IA2 31 (44.29) IA3 23 (32.86) IB 13 (18.57) EGFRm, n(%) 19del 35 (50.00) L858R 35 (50.00) High-risk factors, n(%) solid component ≥10% 11 (15.71) Micropapillary component ≥10% 59 (84.29) complex glands ≥15% 21 (30.00) STAS 18 (25.71) Baseline ctDNA, n(%) Positive 6 (8.57) Negative 64 (91.43) Disease Progression, n(%) Yes 0 (0.00) No 70 (100.00) . TP53 was the most common co-mutation gene, with an incidence of 44.9% (31/70). This was followed by EGFR-other mutations (24.6%,17/70), which were more likely to co-occur with L858R (42.9%, 15/35, P=0.002). Both 1-year and 2-year DFS rates are 100%. At DCO, 7(10%) pts discontinued Osimertinib due to adverse events, and 63 of 70 patients (90%) were continuing osimertinib regimen without disease progression. Six (8.6%) patients had positive ctDNA at baseline. The ctDNA clearance rate was 83.3% (5/6) and 100% (6/6) when ctDNA was evaluated at week 12 and 24, respectively. Conclusions: Osimertinib 80mg orally once daily has shown promising efficacy as adjuvant therapy for completely resected stage I with high-risk factors NSCLC with EGFR mutations. Citation Format: Jiping Xie, Chen Chen, Bin Zhang, Changli Wang, Qiang Zhang, Zhenfa Zhang, Lei Zhang, Shengguang Wang, Xinyue Wang, Richeng Jiang, Dongsheng Yue. Efficacy and safety of osimertinib therapy in high-risk stage I EGFRm NSCLC after R0 resection(OSTAR): A phase II, prospective, single-arm study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT164.