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Updated: Apr 30, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients
J L Kuiper1, D A M Heideman2, E Thunnissen2
1Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
Aim:
Non-small cell lung cancer (NSCLC)-patients with an epidermal growth factor receptor (EGFR)-mutation have median progression-free survival (PFS) of 12 months on tyrosine kinase inhibitors (TKIs). Resistance is mediated by the EGFR T790M-mutation in the majority of patients. Longitudinal follow-up data are lacking. We retrospectively evaluated EGFR-mutated NSCLC-patients who were rebiopsied after TKI-treatment. A subgroup was sequentially rebiopsied along the course of the disease.
Patients And Methods:
Advanced EGFR-mutated NSCLC-patients who had both a pre-TKI biopsy and post-TKI biopsy available were included. Information on treatments and (re)biopsies was collected chronologically. Primary endpoint was the incidence of the T790M-mutation.
Results:
Sixty-six patients fulfilled the inclusion criteria. In first post-TKI biopsies, T790M-mutation was detected in 34 patients (52%) of patients. Twenty-seven patients had subsequent post-TKI rebiopsies with mutation analysis available; in 10 patients (37%) the T790M-status in subsequent post-TKI rebiopsies was not consistent with the T790M-status of the first post-TKI biopsy. Progression free survival (PFS) on TKI-treatment was 12.0 months. Objective response rate on TKI-treatment was 81%. Patients developing T790M-mutation at post-TKI biopsy had longer median PFS compared to T790M-negative patients (14.2 versus 11.1 months respectively (P=0.034)) and longer overall survival (45.9 months versus 29.8 months respectively (P=0.213)). Transformation to SCLC was detected in 1 patient (2%).
Conclusion:
Incidence of T790M-mutation at first post-TKI biopsy in this cohort of EGFR-mutated NSCLC-patients was 52%. Detection of T790M-mutation was not consistent over time; some patients who were T790M-positive at first post-TKI biopsy became T790M-negative in later post-TKI rebiopsies and vice versa. T790M-positive patients showed longer PFS than T790M-negative patients. Whether the low incidence of transformation to SCLC is justifying post-TKI rebiopsy in EGFR-mutated NSCLC-patients with acquired TKI-resistance in regular clinical practice is debatable.
Insights
The EGFR T790M mutation occurs in 52% of non-small cell lung cancer patients after tyrosine kinase inhibitor treatment. This mutation status can change over time, impacting progression-free survival.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) with EGFR mutations typically shows 12-month progression-free survival (PFS) with tyrosine kinase inhibitors (TKIs).
- Acquired resistance to TKIs is often mediated by the EGFR T790M mutation.
- Longitudinal data on TKI resistance mechanisms in NSCLC are limited.
Purpose of the Study:
- To retrospectively evaluate the incidence and consistency of the EGFR T790M mutation in NSCLC patients post-TKI treatment.
- To analyze the impact of T790M mutation status on progression-free survival (PFS) and overall survival.
- To assess the clinical utility of serial rebiopsies in managing acquired TKI resistance.
Main Methods:
- Retrospective analysis of advanced EGFR-mutated NSCLC patients with pre-TKI and post-TKI biopsies.
- Chronological collection of treatment and biopsy data.
- Primary endpoint: incidence of T790M mutation in post-TKI biopsies.
Main Results:
- The T790M mutation was detected in 52% of patients in the first post-TKI biopsy.
- T790M status was inconsistent over time in 37% of patients with serial rebiopsies.
- T790M-positive patients demonstrated significantly longer median PFS (14.2 months) compared to T790M-negative patients (11.1 months).
Conclusions:
- The EGFR T790M mutation is prevalent in 52% of EGFR-mutated NSCLC patients after TKI therapy.
- T790M mutation status is dynamic, with inconsistencies observed in serial biopsies.
- The presence of T790M mutation correlates with improved PFS, but the value of routine post-TKI rebiopsy for resistance monitoring remains debatable due to low SCLC transformation rates.
