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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Molecular testing, treatment patterns, and outcomes in EGFR-mutated non-small cell lung cancer: the PISCES study
Panwen Tian1,2, Lin Wu3, Chengzhi Zhou4
1Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Center/Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Background:
This study investigated molecular testing, treatment patterns, and prognosis in Chinese patients who progressed from first-line (1 L), epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs) therapy, highlighting limited real-world data on clinical practice.
Methods:
Consecutive eligible patients were prospectively enrolled in 16-centers in China. The primary endpoints were second-line (2 L) treatment patterns and clinical outcomes, including median progression-free survival (mPFS) and median overall survival (mOS) from 2 L treatment.
Results:
Overall, 300 patients were enrolled in the study, and among them, 291 patients were included in the Full Analysis Set, and 213(73.2%) underwent molecular testing, after progression from 1 L therapy. 30.5% (65/213) had tissue samples, while 66.7% (142/213) had plasma samples. In tissue and plasma samples, T790M positive rates were 53.8% and 43.7%, respectively. mPFS and mOS for patients with T790M positive who received third generation (3 G) EGFR-TKIs as 2 L therapy were 14.7 months and 32.0 months, respectively. The mPFS for patients with T790M negative who received 3 G EGFR-TKIs, prior EGFR-TKIs plus local therapy, and chemotherapy as 2 L therapy were 7.6 months, 10.2 months, and 4.9 months, respectively. The corresponding mOS for these patients were 21.2 months, 16.6 months, and 15.0 months, respectively. No new safety signal emerged.
Conclusions:
Patients with acquired resistance to first generation (1 G)/second generation (2 G) EGFR-TKIs receiving 3 G EGFR-TKIs, especially T790M positive, showed better clinical outcomes after molecular testing.
Clinical Trial Registration:
The study has been registered at ClinicalTrials.gov (NCT04207775).
Insights
Molecular testing after first-line epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs) therapy is crucial. T790M-positive patients receiving third-generation EGFR-TKIs showed improved outcomes in China.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Research
Background:
- Limited real-world data exists on treatment patterns and prognosis for Chinese patients progressing after first-line epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs) therapy.
- This study addresses the gap by investigating molecular testing, treatment strategies, and outcomes in this patient population.
Purpose of the Study:
- To evaluate second-line (2L) treatment patterns and clinical outcomes in Chinese patients who progressed on first-line (1L) EGFR-TKIs.
- To assess the impact of molecular testing, specifically T790M mutation status, on treatment selection and patient prognosis.
Main Methods:
- Prospective enrollment of eligible patients across 16 centers in China.
- Collection of data on 2L treatment patterns, molecular testing (tissue and plasma), and clinical outcomes, including median progression-free survival (mPFS) and median overall survival (mOS).
Main Results:
- Of 291 patients, 213 underwent molecular testing; T790M mutations were detected in 53.8% (tissue) and 43.7% (plasma).
- T790M-positive patients receiving third-generation (3G) EGFR-TKIs as 2L therapy achieved mPFS of 14.7 months and mOS of 32.0 months.
- T790M-negative patients receiving 3G EGFR-TKIs, prior EGFR-TKIs plus local therapy, or chemotherapy had mPFS ranging from 4.9 to 10.2 months and mOS from 15.0 to 21.2 months.
Conclusions:
- Molecular testing following acquired resistance to first-generation (1G)/second-generation (2G) EGFR-TKIs is valuable.
- Third-generation (3G) EGFR-TKIs demonstrate superior clinical outcomes, particularly in T790M-positive patients, highlighting the importance of targeted therapy guided by molecular profiling.
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