[Search for the T790M mutation: The need to persevere]

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• First- or second-generation EGFR-tyrosine kinase inhibitors (TKIs) are standard first-line treatments for advanced EGFR mutation-positive non-small cell lung cancer.
• Disease progression is common, with 50-60% of cases developing resistance due to the T790M mutation.

Observation:

• Osimertinib (a third-generation EGFR-TKI) is a second-line treatment option, but its use requires T790M mutation identification.
• This report details 7 cases where identifying the T790M mutation necessitated repeated cell-free DNA and/or biopsy analyses over time.
• In some instances, a positive T790M result was confirmed significantly after disease progression was noted during first- or second-generation EGFR-TKI therapy.

Findings:

• Repeated testing for the T790M resistance mutation can yield positive results even after initial negative findings.
• The timing of T790M mutation detection can be delayed, occurring long after disease progression is clinically evident.

Implications:

• This highlights the importance of persistent T790M mutation screening in non-small cell lung cancer patients experiencing progression on EGFR-TKIs.
• Exploring various screening methods for the T790M mutation is encouraged.
• Perseverance in seeking the T790M mutation is advised when no other resistance mechanisms are identified.