Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations. (October 2022)

• Record Type: Journal Article
• Authors: Hsu, Ping-Chih; Chang, John Wen-Cheng; Chang, Ching-Fu; Huang, Chen-Yang; Yang, Cheng-Ta; Kuo, Chih-Hsi Scott; Fang, Yueh-Fu; Wu, Chiao-En
• Is Part Of: Therapeutic advances in respiratory disease. Volume 16(2022)
• Publication Date: 2022-10
• Subjects: EGFR-tyrosine kinase inhibitors -- epidermal growth factor receptor mutation -- lung cancer -- osimertinib -- T790M mutation; Respiratory organs -- Diseases -- Periodicals; Respiratory agents -- Periodicals; Pulmonary pharmacology -- Periodicals; Respiratory Tract Diseases -- Periodicals; Respiratory System Agents -- therapeutic use -- Periodicals; Respiratory Tract Diseases -- drug therapy -- Periodicals; Lung Diseases -- drug therapy -- Periodicals; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Agents respiratoires -- Périodiques; Pharmacologie pulmonaire -- Périodiques; 616.2005
• DOI: 10.1177/17534666221132731
• Languages: English
• ISSNs: 1753-4658

Abstract

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non–small cell lung cancer (NSCLC) patients. Osimertinib is an effective therapy for NSCLC patients with acquired resistance due to T790M mutation after first- and second-generation EGFR-TKI treatment. This study aimed to analyze the clinical outcomes of sequential therapy following first-line EGFR-TKIs and the predictive factors of an acquired T790M mutation. Methods: Between January 2014 and December 2018, data from 2190 advanced NSCLC patients with common EGFR mutations (exon 19 deletion and L858R) receiving first- and second-generation EGFR-TKIs in Linkou, Kaohsiung, Chiayi and Keelung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Results: Until August 2021, among 1943 patients who experienced progressive disease, 526 underwent T790M mutation tests, and their T790M-positive rate was 53.6%. Exon 19 deletion mutation and progression-free survival (PFS) of >12 months were positively associated with secondary T790M mutation. Different first-line first- and second-generation EGFR-TKI therapies did not affect the appearance of acquired T790M mutations. The median overall survival (OS) was 58.3 [95% confidence interval (CI): 49.0–67.5] months among the patients with T790M mutation who received second-line osimertinib therapy compared with 31.0 (95% CI: 27.5–34.5) months among the patients without T790M mutation who received chemotherapy alone. The multivariate analysis showed that a poor performance status (score: >2), nonadenocarcinoma histology, stage IV cancer, liver metastasis, brain metastasis, PFS while on first-line EGFR-TKIs, and subsequent chemotherapy without third-generation EGFR-TKIs were significant independent unfavorable prognostic factors for OS. Conclusion: This study demonstrated the efficacy of first-line EGFR-TKIs and sequential osimertinib therapy. The results of our study suggest that T790M mutation tests are important for the use of subsequent osimertinib, which yielded favorable survival outcomes.