A real-world study on first-line (1L) treatment for 46 advanced lung adenocarcinoma patients harbouring epidermal growth factor 20 insertion mutation (EGFR ex20ins).

e20652 Background: EGFR ex20ins is a rare mutation in lung adenocarcinoma. For this mutation, 1L standard of care(SOC) are mainly based on platinum - based chemotherapy. In recent years, with the publication of the results of numerous clinical studies focusing on novel targeted drugs, surprising efficacy has been demonstrated. However, real-world studies comparing the efficacy of novel targeted drug-based therapies(NTT) and SOC treatments are still lacking, especially in 1L treatment. Methods: The CAPTRA-Lung (NCT03334864) database was used to retrieve patients with EGFR ex20ins-mutated advanced adenocarcinoma from 2018 to 2025 in Shanxi province cancer hospital. In SOC cohort, patients received platinum-based chemotherapy with or without anti-angiogenic/immune inhibitor. In NTT cohort, patients received sunvozertinib, furmonertinib or combination therapy of JMT101 and osimertinib. 1L progression free survival (PFS) was the primary endpoint. The follow-up deadline was January 15, 2025. Results: Forty-six patients were involved in this study. Among them, 21 out of 46 (45.7%) were detected by next-generation sequencing (NGS) , 54.3% by polymerase chain reaction(PCR). Median age was 59.2 years [56.7-61.8]; 43.5% of patients were female and 63% non-smoker; 89.1% of patients were at stage IV when diagnosed; most common baseline metastatic sites were bone (52.2%), pleura (39.1%) and brain (26.1%). Mutation subtypes could be analyzed in 43.5% of patients, which were near-loop (30.4%) , far-loop （8.7%) and αC-helix (4.3%) in sequence. NTT cohort (n=14) consisted of sunvozertinib (n=5; 35.7%), furmonertinib (n=5; 35.7%) and combination therapy of JMT101 and osimertinib (n=4; 28.6%). SOC cohort (n=32) constituted platinum-based chemotherapy (n=17; 53.1%) and platinum-based chemotherapy plus anti-angiogenic drugs (n=10; 31.3%) or immune inhibitors (n=4;12.5%). One patient (3.1%) received platinum based-chemotherapy, immune inhibitor and anti-angiogenic drug at the same time. One patients who received furmonertinib was excluded from efficacy analysis for starting 1L treatment one day before the data cut-off in NTT cohort. The median PFS was 18.0 months (95% CI, 3.1-32.9) for NTT cohort compared with 7.0 months (95% CI, 3.8-10.2) for SOC cohort. Compared with SOC cohort, NT cohort significantly prolonged 1L PFS (P=0.018). In addition, most of patients in NTT cohort participated in clinical trials. In NTT cohort, TRAEs could be analyzed in 9 out of 16. Grade of all TRAEs were less than 3, mainly including rash (44%), facial pigmentation(33%) and weight loss(33%). No one in NTT cohort was led to dose reduction or discontinuation because of TRAEs. Conclusions: For advanced lung adenocarcinoma patients harbouring EGFR ex20ins, novel targeted drug-based therapies represented an effective treatment option and were well tolerated.