Importance of repeat tissue biopsy and tissue-based epidermal growth factor receptor T790M testing in progressed nonsmall cell lung carcinoma patients upon negative plasma genotyping for selection of third-generation tyrosine kinase inhibitor therapy: A case study

R Mistry, A Patil

Indian Journal of Cancer 2017 54(5):65-66

Resistance to 1st or 2nd generation epidermal growth factor receptor (EGFR) - tyrosine kinases (TKIs) develops predominantly due to an acquired mutation, EGFR T790M. Third-generation EGFR-TKIs have demonstrated potent activity against TKI resistance mediated by EGFR T790M. Thus, it become critical to identify T790M mutation on disease progression. Analysis of tumor tissue biopsy material is considered as gold standard for mutation detection. However, lung re-biopsy in a progressed patient involves several challenges – access to tumor, patient's willingness, safety, cost. Minimally invasive plasma circulating tumor DNA (ctDNA) evolved as an alternative for detection of EGFR T790M mutation when tumor genotyping is not feasible. Although a positive T790M result from ctDNA analysis is actionable, caution should be exercised in interpreting negative plasma results. A negative result may imply the absence of a mutation or merely that a patient's tumor is not shedding ctDNA at detectable levels, thus necessitating a confirmatory tissue biopsy to rule out a false negative plasma result. In this case report, we described a 78-year-old female who underwent a reflexed tumor biopsy and tissue based testing upon negative plasma genotyping. Our case report exhibited the importance to follow proposed T790M plasma testing algorithm to screen eligible patients for 3rd generation TKI therapy.

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