Related Experiment Video
Updated: Dec 3, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Integrated histological and molecular analyses of rebiopsy samples at osimertinib progression improve
Jiang-Tao Cheng1, Yi-Hui Yao1, Yu-Er Gao1
1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China; Cancer Center, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Background:
This single-center retrospective cohort study sought to investigate the impact of rebiopsy analysis after osimertinib progression in improving the survival outcomes.
Methods:
Eighty-nine patients with EGFR T790M-positive advanced NSCLC who received second- or further-line osimertinib between January 2017 and July 2019 were included in this study. The co-primary study endpoints were post-progression progression-free survival (pPFS), defined as the time from osimertinib progression until progression from further-line treatment, and post-progression overall survival (pOS), defined as the time from osimertinib progression until death or the last follow-up date.
Results:
Pairwise analysis revealed that receiving targeted therapy as further-line treatment after osimertinib progression did not statistically improve the pPFS (P = 0.285) or the pOS (P = 0.903) compared to chemotherapy. However, patients who submitted rebiopsy samples at osimertinib progression for histological and molecular analyses, particularly those who had actionable markers and received highly matched therapy, had significantly longer pPFS and pOS as compared to those who received low-level matched therapy (pPFS = 10.0 m vs. 4.1 m, P = 0.005; pOS = 19.4 m vs. 10.0 m, P = 0.023), unmatched therapy (pPFS = 10.0 m vs. 4.7 m, P = 0.009; pOS = 19.4 m vs. 7.0 m, P = 0.001), and those without rebiopsy data (Rebiopsy vs Non-rebiopsy; pPFS = 6.1 m vs. 3.3 m, P = 0.014; pOS = 11.7 m vs. 6.8 m, P = 0.011).
Conclusion:
Our real-world cohort study demonstrates that integrated histological and molecular analyses of rebiopsy specimens after osimertinib progression could provide more opportunities for individualized treatments to improve the post-progression survival of patients with advanced NSCLC. Our findings provide clinical evidence that supports the inclusion of NGS-based analysis of rebiopsy specimens as standard-of-care after osimertinib progression and warrants further prospective evaluation.
Insights
Rebiopsy analysis after osimertinib progression in advanced non-small cell lung cancer (NSCLC) improves survival outcomes. Integrated histological and molecular analysis of rebiopsy specimens offers personalized treatment opportunities, enhancing post-progression survival.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Research
Background:
- Retrospective cohort study investigating rebiopsy impact post-osimertinib progression in advanced non-small cell lung cancer (NSCLC).
- Focus on improving survival outcomes for patients with EGFR T790M-positive NSCLC.
Purpose of the Study:
- To evaluate the effect of rebiopsy analysis on survival after osimertinib progression.
- To determine if histological and molecular analysis of rebiopsy specimens can guide subsequent treatment decisions.
Main Methods:
- Retrospective analysis of 89 patients with EGFR T790M-positive advanced NSCLC treated with osimertinib.
- Co-primary endpoints: post-progression progression-free survival (pPFS) and post-progression overall survival (pOS).
- Comparison of outcomes based on rebiopsy status and targeted therapy matching.
Main Results:
- Targeted therapy after progression did not significantly improve pPFS or pOS compared to chemotherapy.
- Rebiopsy with integrated histological and molecular analysis significantly improved pPFS and pOS.
- Patients receiving highly matched therapy based on rebiopsy data showed superior outcomes.
Conclusions:
- Integrated analysis of rebiopsy specimens after osimertinib progression enhances individualized treatment strategies.
- Supports the routine use of Next-Generation Sequencing (NGS)-based rebiopsy analysis as standard of care.
- Highlights the potential for improved post-progression survival in advanced NSCLC.
