Real-world efficacy of low dose osimertinib as second-line treatment in patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer

Poh, Mau Ern and Balakrishnan, Sivasubramaniam and Tan, Sin Nee and Abidin, Muhammad Adil Zainal and Liam, Chong Kin and Tan, Jiunn Liang and Pang, Yong Kek and Alaga, Arvindran and Tho, Lye Mun and How, Soon Hin (2024) Real-world efficacy of low dose osimertinib as second-line treatment in patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Translational Lung Cancer Research, 13 (7). pp. 1649-1659. ISSN 2218-6751, DOI https://doi.org/10.21037/tlcr-24-243.

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Official URL: https://doi.org/10.21037/tlcr-24-243

Abstract

Background: Response rates of epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) to lower doses of osimertinib 20 mg once daily (OD) and 40 mg OD] are similar to those of the recommended dose of 80 mg OD, but there is a lack of real-world evidence on the effect of the lower doses of osimertinib on survival outcomes. We conducted this study to assess the efficacy and safety of lower osimertinib doses for patients with EGFR-mutated advanced NSCLC whose disease had progressed on earlier generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world clinical practice. Methods: This multicenter, retrospective study included patients with EGFR-mutated advanced NSCLC treated with low doses of osimertinib after failing first- or second-generation EGFR TKIs due to acquired T790M mutation. Data on demographics, staging, treatment history, best overall response rate (ORR) based on RECIST 1.1, and adverse events (AEs) were collected from the patients' case notes. Descriptive data were described in percentages and medians. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Of the 22 patients studied males =8 and females =14; Eastern Cooperative Oncology Group (ECOG) 1 or 2 =7 and ECOG 3 or 4 =15], 45.5% were on 40 mg OD, 31.8% were on 80 mg every other day (EOD), and 22.7% on 40 mg EOD. First-line EGFR TKIs used included afatinib, erlotinib, and gefitinib. The ORR with lower doses of second-line osimertinib was 77.3%. Overall, the median PFS was 10.0 months 95% confidence interval (CI): 8.6-11.4] and median OS was 13.0 months (95% CI: 9.4-16.6). In patients with ECOG 1 or 2, the median PFS was 18.0 months (95% CI: 5.8-30.2) and the median OS was not reached at the time of analysis. In patients with poor ECOG performance status of 3 and 4, good survival outcomes were also seen with a median PFS of 7.0 months (95% CI: 4.7-9.3) and median OS of 10.0 months (95% CI: 7.5-12.5). All AEs except one case of paronychia were Grade 1. There were no Grade 3 or 4 AEs. Conclusions: Treatment with low dose osimertinib demonstrated good efficacy and tolerability in EGFRmutated advanced NSCLC patients who failed first-line treatment with first- or second-generation EGFR TKIs due to T790M mutation.

Item Type: Article
Funders: Malaysian Thoracic Society
Uncontrolled Keywords: Adverse event (AE); overall response rate (ORR); overall survival (OS); progression-free survival (PFS); tyrosine kinase inhibitor (TKI)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine > Medicine Department
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 27 Mar 2025 07:49
Last Modified: 27 Mar 2025 07:49
URI: http://eprints.um.edu.my/id/eprint/46766

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