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Real-World EGFR T790M Testing in Advanced Non-Small-Cell Lung Cancer: A Prospective Observational Study in Japan
Takashi Seto1, Naoyuki Nogami2, Nobuyuki Yamamoto3
1Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. tseto@nk-cc.go.jp.
Introduction:
Approximately one-half of patients with epidermal growth factor receptor (EGFR) mutation-positive advanced/metastatic non-small-cell lung cancer (NSCLC) develop resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) due to a secondary T790M mutation. This study investigated the pattern of T790M testing after EGFR TKI treatment in a real-world setting in Japan.
Method:
This prospective observational study enrolled patients with EGFR mutation-positive advanced/metastatic NSCLC who reported disease progression during treatment with first- or second-generation EGFR TKIs. Data regarding sampling methods for T790M mutation testing (plasma sample, cytology or tissue biopsy) and the treatment strategies after disease progression were recorded prospectively.
Results:
A total of 236 patients were included in the study (female, 67.4%; median age, 73.0 years), and 205 patients (86.9%) underwent rebiopsy by any of the three possible methods: plasma sampling in 137 patients (58.1%) and tissue/cytology sampling in 68 patients (28.8%) during the first rebiopsy. Overall, 80.6% of the tissue/cytology samples contained tumor cells, and 40% of these samples were positive for the T790M mutation. T790M mutations were detected in only 19.7% of plasma samples. Of the 199 patients who underwent T790M testing, 61 (30%) tested positive, and 56 (91.8%) subsequently received osimertinib.
Conclusion:
Among the 87% of Japanese patients who underwent rebiopsy after progressing on treatment with a first- or second-generation EGFR TKI, approximately 30% tested positive for the T790M mutation and were eligible to receive osimertinib. Although plasma sampling is non-invasive, this rebiopsy method is less sensitive for T790M detection compared with tissue or cytology sampling (UMIN identifier: UMIN000024928).
Funding:
AstraZeneca Japan.
Insights
Approximately 87% of Japanese patients with EGFR-mutated non-small-cell lung cancer who progressed on TKIs underwent rebiopsy. About 30% tested positive for the T790M mutation, enabling osimertinib treatment, with tissue biopsy showing higher sensitivity than plasma testing.
Area of Science:
- Oncology
- Medical Genetics
- Pharmacology
Background:
- Non-small-cell lung cancer (NSCLC) with EGFR mutations often develops resistance to EGFR tyrosine kinase inhibitors (TKIs).
- The T790M mutation is a common mechanism of acquired resistance to first- and second-generation EGFR TKIs.
- Investigating T790M testing patterns is crucial for guiding subsequent treatment strategies in advanced/metastatic NSCLC.
Purpose of the Study:
- To examine the real-world patterns of T790M mutation testing in Japanese patients with EGFR-mutated advanced/metastatic NSCLC following disease progression on EGFR TKIs.
- To compare the sensitivity of different rebiopsy methods (plasma, tissue, cytology) for detecting the T790M mutation.
- To assess the proportion of patients eligible for third-generation EGFR TKI therapy (osimertinib) based on T790M testing results.
Main Methods:
- Prospective observational study of patients with EGFR mutation-positive advanced/metastatic NSCLC who progressed on first- or second-generation EGFR TKIs.
- Data collection on sampling methods for T790M mutation testing: plasma, tissue biopsy, or cytology.
- Prospective recording of treatment strategies implemented after disease progression.
Main Results:
- Out of 236 patients, 86.9% underwent rebiopsy. Plasma sampling was used in 58.1% and tissue/cytology in 28.8% for the first rebiopsy.
- T790M mutations were detected in 40% of tissue/cytology samples but only 19.7% of plasma samples.
- Of 199 patients tested, 30% were T790M positive, with 91.8% subsequently receiving osimertinib.
Conclusions:
- Approximately 87% of Japanese patients with EGFR-mutated NSCLC progressing on first- or second-generation EGFR TKIs underwent rebiopsy.
- Around 30% of these patients tested positive for the T790M mutation, qualifying them for osimertinib.
- Tissue or cytology sampling demonstrated higher sensitivity for T790M detection compared to plasma-based testing, despite plasma being less invasive.
