Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA
J Remon1, C Caramella2, C Jovelet3
1Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
Background:
Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients.
Material And Methods:
ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA.
Results:
The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively.
Conclusion(S):
ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue.
Insights
Liquid biopsy detecting T790M mutation in EGFR-mutant NSCLC patients shows efficacy with osimertinib treatment. This approach offers a viable alternative to tissue biopsy for guiding therapy in advanced lung cancer.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) often involves the T790M mutation.
- Approximately 50% of patients develop this resistance, necessitating alternative treatment strategies.
- Osimertinib is the established standard of care for T790M-positive NSCLC.
Purpose of the Study:
- To evaluate the efficacy of osimertinib in advanced EGFR-mutant NSCLC patients.
- To assess the utility of T790M mutation detection in circulating tumor DNA (ctDNA) as a surrogate for tissue biopsy.
- To determine response rates and progression-free survival (PFS) using ctDNA-based T790M testing.
Main Methods:
- A cohort of 48 advanced EGFR-mutant NSCLC patients with acquired resistance to TKIs were analyzed.
- ctDNA T790M mutational status was assessed using the Inivata InVision™ (eTAm-Seq™) assay.
- Patients with ctDNA T790M-positive status received osimertinib 80 mg daily, and outcomes were evaluated by RECIST 1.1 criteria.
Main Results:
- The T790M mutation was detected in ctDNA in 50% of the NSCLC patients studied.
- Among assessable patients, osimertinib achieved a 62.5% partial response rate and 37.5% stable disease rate.
- Median PFS was not reached at 8 months median follow-up, with 6- and 12-month PFS rates of 66.7% and 52%, respectively.
Conclusions:
- ctDNA analysis is a reliable surrogate marker for T790M mutation detection, comparable to tumor tissue biopsy.
- Liquid biopsy provides a non-invasive method for identifying patients eligible for osimertinib treatment.
- This approach supports personalized therapy selection in advanced EGFR-mutant NSCLC.
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