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Updated: Sep 27, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
First and repeat rebiopsy for detecting EGFR T790M mutation in non-small-cell lung cancer: CS-Lung-003 prospective
Kenichiro Kudo1,2, Kazuya Nishii2,3, Go Makimoto2,3
1Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan.
Purpose:
Osimertinib is still essential for the treatment of epidermal growth factor receptor (EGFR)-T790M-positive non-small-cell lung cancer (NSCLC) even in a relapsed setting, which suggests the importance of rebiopsy. The clinical value of repeat rebiopsy in patients with NSCLC who are T790M-negative on a first rebiopsy remains unclear. In this study, we examined the status of the first rebiopsy and evaluated the frequency of repeat rebiopsy of T790M-negative tumors detected by the first rebiopsy.
Methods:
We reviewed 144 patients with NSCLC with major EGFR mutations, but not T790M, who received first- or second-generation EGFR tyrosine kinase inhibitors (TKIs), registered in the prospective, umbrella-type lung cancer patient registry (CS-Lung-003).
Results:
Overall, 63 patients (44%) underwent the first rebiopsy. In the first rebiopsy, 51 (81%) and 12 (19%) of 63 underwent histological/cytological rebiopsy and liquid biopsy with the blood sampling, respectively. In the repeat rebiopsy, 23 (85%) and 4 (15%) of 27 underwent histological/cytological rebiopsy and liquid biopsy, respectively. The most frequently rebiopsied site was a pulmonary lesion (n = 24, 38.7%). Overall, 29 (46.0%) of 63 patients harbored the T790M mutation. Interestingly, a high detection rate of cancer cells did not necessarily indicate a high detection rate of the T790M mutation (p < 0.01). Among 34 patients with T790M-negative tumors confirmed on the first rebiopsy, 20 (58.8%) underwent repeat rebiopsies following interval therapy, revealing that seven (36.8%) had T790M-positive tumors. Osimertinib yielded median progression-free survival of 11.8 and 16.2 months in patients with the 790M mutation detected by the first rebiopsy and repeat rebiopsy, respectively.
Conclusion:
In our prospective cohort, the T790M mutation was detected in 46% of patients who underwent the first rebiopsy. Repeat rebiopsy may increase the ability to detect the T790M mutation positivity rate.
Insights
Repeat rebiopsy is crucial for detecting the T790M mutation in non-small-cell lung cancer (NSCLC) patients. This study shows that repeat biopsies can increase the T790M mutation positivity rate, improving treatment selection.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osimertinib is vital for EGFR-T790M-positive non-small-cell lung cancer (NSCLC), even after relapse.
- The utility of repeat rebiopsy in T790M-negative NSCLC patients after initial rebiopsy is not well-defined.
Purpose of the Study:
- To assess the clinical value of repeat rebiopsy in NSCLC patients.
- To evaluate the frequency and outcomes of repeat rebiopsy in T790M-negative tumors identified by first rebiopsy.
Main Methods:
- A prospective registry (CS-Lung-003) of 144 NSCLC patients with major EGFR mutations (excluding T790M) treated with first- or second-generation EGFR TKIs was reviewed.
- Analysis included first and repeat rebiopsy data (histological/cytological and liquid biopsy).
Main Results:
- 46% of patients (29/63) had T790M mutation detected on first rebiopsy.
- Among 34 T790M-negative patients on first rebiopsy, 20 underwent repeat rebiopsy, revealing T790M positivity in 7 (36.8%).
- Repeat rebiopsy improved median progression-free survival with Osimertinib from 11.8 to 16.2 months.
Conclusions:
- The T790M mutation was detected in 46% of NSCLC patients undergoing first rebiopsy.
- Repeat rebiopsy significantly increases the detection rate of T790M mutations.
- Repeat rebiopsy is valuable for optimizing treatment strategies in NSCLC.
