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EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth
Anne C Chiang1, Ancilla W Fernandes2, Melissa Pavilack2
1Yale School of Medicine, 20 York Street, New Haven, CT, 06510, USA. anne.chiang@yale.edu.
Background:
The objective of this study was to investigate real-world EGFR mutation testing in patients with metastatic non-small cell lung cancer (NSCLC) upon progression on first-/second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI), and subsequent treatments received.
Methods:
Flatiron Health electronic health records-derived database was used to identify adult patients with metastatic NSCLC treated with first-/second-generation EGFR-TKI from 11/2015-09/2017, with start of first EGFR-TKI defined as the index date. Patients were stratified by receipt of EGFR-TKI as first-line (1 L) or later-line (2 L+) treatment. Mutation testing and subsequent therapies following first-/second-generation EGFR-TKI were described.
Results:
Overall, 782 patients (1 L = 435; 2 L+ =347) were included. Median age was 69.0 years, 63.6% were female, 56.3% were white, 87.1% were treated in community-based practices, and 30.1% of patients died during the study period; median follow-up was 309.0 days. Among the 294 (1 L = 160; 2L+ =134) patients who received subsequent therapies, treatments included chemotherapy only (1 L = 15.6%; 2L+ =21.6%), immunotherapy only (1 L = 13.8%; 2 L+ =41.0%), and targeted therapies (1 L = 70.0%; 2 L+ =36.6%). Specifically, 40 (25.0%) 1 L patients and 7 (5.2%) 2 L+ patients received osimertinib as subsequent therapy. Before the start of subsequent therapy, EGFR T790M resistance mutation testing was performed in 88 (29.9%) patients (1 L = 63 [39.4%]; 2 L+ =25 [18.7%]). Of these patients, 25 (28.4%) were T790M positive, among whom 24 (96.0%) received osimertinib.
Conclusions:
A third of patients received subsequent therapies on disease progression; only 30% of these were tested for EGFR-TKI resistance mutation, prior to receiving subsequent therapies. These results highlight the importance of choosing treatments in the 1 L setting that optimize benefits for patients with EGFR-mutated NSCLC.
Insights
Real-world data shows limited EGFR T790M mutation testing in metastatic non-small cell lung cancer (NSCLC) patients progressing on first-/second-generation EGFR-tyrosine kinase inhibitors (TKIs). This highlights a gap in guiding subsequent treatment decisions for optimal patient benefit.
Area of Science:
- Oncology
- Medical Informatics
Background:
- Metastatic non-small cell lung cancer (NSCLC) is a significant health concern.
- Epidermal growth factor receptor (EGFR) mutations are key drivers in NSCLC.
- First- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) are standard treatments, but resistance develops.
Purpose of the Study:
- To evaluate real-world EGFR mutation testing patterns after progression on first-/second-generation EGFR-TKIs in metastatic NSCLC.
- To describe subsequent treatment modalities utilized in this patient population.
- To identify the frequency of T790M resistance mutation testing and its impact on treatment selection.
Main Methods:
- A retrospective analysis of the Flatiron Health electronic health records database.
- Inclusion of adult patients with metastatic NSCLC treated with first-/second-generation EGFR-TKIs between November 2015 and September 2017.
- Stratification of patients into first-line (1L) and later-line (2L+) treatment groups.
Main Results:
- Out of 782 patients, 294 received subsequent therapies. Only 29.9% of patients undergoing subsequent therapy were tested for the EGFR T790M resistance mutation prior to treatment initiation.
- Among those tested, 28.4% were T790M positive, and 96.0% of these received osimertinib.
- Subsequent treatments varied, including chemotherapy, immunotherapy, and targeted therapies, with notable differences between 1L and 2L+ groups.
Conclusions:
- A significant proportion of patients progressing on initial EGFR-TKIs did not undergo T790M resistance mutation testing before subsequent therapy.
- The low rate of testing suggests potential missed opportunities for targeted treatment with osimertinib.
- Optimizing treatment selection in the first-line setting is crucial for patients with EGFR-mutated NSCLC.
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