4.5 Article

Patterns of progression on osimertinib in EGFR T790M positive NSCLC: A Swiss cohort study

期刊

LUNG CANCER
卷 130, 期 -, 页码 149-155

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ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2019.02.020

关键词

NSCLC advanced; Osimertinib; Oligoprogression; Local ablative therapy

资金

  1. AstraZeneca

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Introduction: Osimertinib is an EGFR tyrosine kinase inhibitor (TKI) with antitumor activity in non-small cell lung cancer (NSCLC) with EGFR T790 M mutations. The incidence of oligo-progression (PD) on osimertinib is unknown. Methods: We retrospectively analyzed 50 pre-treated EGFR T790M-positive NSCLC patients treated with osimertinib at seven Swiss centers. Oligo-PD was defined as PD in <= 5 lesions. Mutational profiling of pre- and post-osimertinib tumor samples was performed. Results: Median age was 62 years (37-89), 64% were females, 86% had a PS <= 1, 54%/13% were never/current smokers. Median follow-up was 15.3 (IQR: 8.6-21.6) months. Overall response rate was 80%, median progression -free survival 12.1 months (95% CI 8.3-18.3), median overall survival 28 months (95% CI 20.2-not reached [NR]) and median treatment duration 18.8 months (95%CI 16-8-NR). PD occurred in 36 patients (72%). 73% had oligo-PD. Median osimertinib treatment duration in patients with oligo-PD was 19.6 vs. 7 months if systemic PD (p = 0.007). The number of progressive lesions in patients with oligo-PD was 1 (27%), 2 (35%) and 3-5 (39%). Sites of PD included lungs (56%), bones (44%), and brain (17%). Sixteen patients with oligo-PD continued treatment with osimertinib for a median of 6.7 months beyond PD. Thirteen received local ablative treatment (LAT). In pre- and post-PD tumor tissue multiple molecular alterations were detected. Conclusion: In patients with acquired resistance to osimertinib, we observed a high rate (73%) of oligo-PD. Outcomes of patients receiving LAT were favorable, supporting the concept of osimertinib treatment beyond progression in combination with LAT of progressing lesions.

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