Complex EGFR mutations with secondary T790M mutation confer shorter osimertinib progression-free survival and overall survival in advanced non-small cell lung cancer. (July 2020)

• Record Type: Journal Article
• Authors: Lin, Yen-Ting; Tsai, Tzu-Hsiu; Wu, Shang-Gin; Liu, Yi-Nan; Yu, Chong-Jen; Shih, Jin-Yuan
• Is Part Of: Lung cancer. Volume 145(2020)
• Page Start: 1
• Page End: 9
• Publication Date: 2020-07
• Subjects: EGFR repidermal growth factor receptor -- TKI tyrosine kinase inhibitor -- NSCLC non-small cell lung cancer -- Cobas V2 Roche cobas EGFR Mutation Test V2 -- MALDI-TOF MS matrix-assisted laser desorption ionization-time of flight mass spectrometry -- RT-PCR reverse transcription polymerase chain reaction -- NGS next-generation sequencing -- PFS progression-free survival -- NTUH National Taiwan University Hospital -- ECOG Eastern Cooperative Oncology Group -- IQR interquartile range -- TTF time to treatment failure -- OS overall survival -- CI confidence interval -- aHR adjusted hazard ratio; Uncommon EGFR mutation -- Compound EGFR mutations -- Acquired T790M -- Treatment outcome -- Osimertinib resistance; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2020.04.022
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Osimertinib is active against lung cancer with activating EGFR mutation and T790M. Its efficacy against complex EGFR mutations with T790M has not been evaluated yet. We found osimertinib response rate was only 27% for complex mutations with T790M. The progression-free survival and overall survival were also significantly shorter. Whether osimertinib is the first choice for this population may be questionable. Abstract: Objectives: Osimertinib is active against epidermal growth factor receptor ( EGFR ) T790M-mutated non-small cell lung cancer (NSCLC). However, its efficacy against complex EGFR mutations with T790M has not been evaluated. Materials and methods: In order to detect complex EGFR mutations, we consecutively sequenced cancer tissues by RNA reverse transcription polymerase chain reaction. Patients with advanced NSCLC with activating EGFR mutation and secondary T790M who received osimertinib were enrolled. Patients' clinicopathologic characteristics, prior treatment details, and osimertinib treatment outcomes were analyzed. Results: Totally, 165 sequenced patients were analyzed. Eleven (7%) of them had complex EGFR mutations with T790M. The osimertinib response rate was 27%. They had a shorter progression-free survival (PFS) (median, 2.9 and 9.7 months, p < 0.001) and overall survival (OS) (median, 17.8 and 31.0 months, p = 0.01) than patients with a single EGFR mutation with T790M. After osimertinib failure, seven patients received rebiopsy with molecular analysis. Four lost the T790M, two transformed to small cell and one acquired C797S. Moreover, taking the median as the demarcation, patients received shorter prior EGFR tyrosine kinase inhibitor (TKI) treatment duration had a shorter osimertinib PFS (median, 7.3 and 13.8 months, p < 0.001) and OS (median, 21.5 and 36.7 months, p = 0.003). Multivariate Cox regression analysis confirmed complex EGFR mutations and prior EGFR TKI treatment duration were independent factors for osimertinib PFS and OS. Conclusions: Complex EGFR mutations and shorter prior EGFR TKI treatment duration may confer shorter osimertinib PFS and OS in advanced NSCLC with secondary T790M mutation.