Real‐world outcomes of NSCLC patients receiving tissue or circulating tumor DNA‐guided osimertinib treatment

Abstract

Background Osimertinib yields significant tumor responses and durations of progression‐free survival (PFS) in patients with acquired T790M mutations. However, the evidence supporting liquid biopsy‐guided treatment is still limited. This study examined the real‐world benefits of osimertinib in patients with tissue or plasma T790M mutations. Methods From January 2016 to June 2018, a total of 183 non‐small‐cell lung cancer patients were enrolled. The presence of the T790M mutation was assessed by either tissue or plasma. The PFS, overall survival, and tumor response rates of the patients were calculated and compared with those of previous clinical trials. Results T790M mutations were detected in 51.5% of the patients, including 64 of 140 (45.7%) who underwent liquid biopsies and 23 of 29 (79.3%) who underwent tumor biopsies. After excluding those in clinical trials, 46 patients received osimertinib, including 33 with positive plasma and 13 with positive tissue results for T790M mutations. The median PFS was 11.3 months (interquartile range: 5.2‐NR) in all the T790M‐positive patients and 10.1 months (interquartile range: 5.9‐NR) in the plasma T790M‐positive patients. The overall survival, meanwhile, was not reached, whereas the one‐year survival rate was 66.1% in all the patients and 61.4% in those who were plasma T790M‐positive. The objective response rate and disease control rate were 37.8% and 91.9% in all the patients and 34.6% and 92.3% in the plasma T790M‐positive group, respectively. Using a Cox proportional hazards regression, we determined that male gender was a poor prognostic factor for PFS. Conclusions In this retrospective real‐world analysis, it was determined that both tissue and plasma T790M mutations can be used to guide treatment with osimertinib. Similar disease control rates and survival durations were observed in comparison to those of phase 3 clinical trials.

Machine Learning-Based CT Radiomics Analysis for Prognostic Prediction in Metastatic Non-Small Cell Lung Cancer Patients With EGFR-T790M Mutation Receiving Third-Generation EGFR-TKI Osimertinib Treatment

“…At present, only a few researchers had explored clinical factors that could potentially affect the therapeutic efficacy of the osimertinib treatment. Factors including smoking history, high N stage and poor performance score were related to an unfavorable prognosis in the osimertinib therapy ( 5 – 8 ). In the current study, smoking history and N stage were not associated with patients’ outcomes in osimertinib treatment.…”

“…The prognostic value of other clinical factors such as age and gender remain inconsistent among various researches. There are studies showing that young age is related to a favorable ( 23 ), unfavorable ( 24 ) prognosis or no prognostic significance ( 25 ), and the same controversial reports for gender ( 5 , 25 ). Besides, the PFS of the first-line TKIs treatment may also impact the efficacy of the sequential osimertinib therapy ( 26 ).…”

“…Several studies explored factors that can potentially affect the treatment efficacy of osimertinib in NSCLC patients. Clinical factors including male gender, smoking history, high N stage and poor performance score were associated with poor outcomes in osimertinib treatment ( 5 – 8 ).…”

Detection of EGFR Mutations in Cerebrospinal Fluid of EGFR-Mutant Lung Adenocarcinoma With Brain Metastases

“…The EGFR T790M mutation can be detected accurately by liquid biopsy, and the presence of any detectable T790M ctDNA may be clinically relevant ( 29 , 30 ). T790M status by liquid biopsy is well correlated with the response of third-generation TKIs ( 12 , 31 , 32 ). Dynamic repeat testing may provide more information about the mechanism of resistance.…”

Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation

“…Circulating tumor cells (CTCs), cell free DNA containing circulating tumor DNA (cfDNA, ctDNA), extracellular vesicles (EVs), cell free microRNAs, and tumor educated platelets (TEP) are among the circulating biomarkers considered to contain tumor information [ 8 , 9 , 10 ]. In the past decade, research on liquid biopsies for LCa has significantly increased, becoming a non-invasive complement to the traditional tissue biopsies, and leading to several clinical validation studies, mostly focused on CTCs and ctDNA [ 11 , 12 , 13 ].…”