Missed clinical benefit due to false negatives in testing for EGFR T790M mutations in non-small cell lung cancer. (2016)

• Record Type: Journal Article
• Authors: Hart, Meaghan C.; Schrock, Alexa B.; Ou, Sai-Hong Ignatius; Raez, Luis E.; Jhangiani, Haresh S.; Ross, Jeffrey S.; Stephens, Philip J.; Miller, Vincent A.; Ali, Siraj M.
• Is Part Of: Cancer treatment and research communications. Number 9(2016)
• Page Start: 131
• Page End: 133
• Publication Date: 2016
• Subjects: Non-small cell lung cancer -- EGFR T790M -- Osimertinib -- Comprehensive genomic profiling -- Third-generation pyrimidine-based tyrosine kinase inhibitors
• DOI: 10.1016/j.ctarc.2016.08.010
• Languages: English
• ISSNs: 2468-2942

Abstract

Abstract: Third-generation irreversible epidermal growth factor receptor (EGFR) inhibitors have shown clinical benefit for non-small cell lung cancer (NSCLC) patients with T790M resistance mutations, and one inhibitor, osimertinib, recently received FDA-approval in this population. We present three NSCLC patients with low frequency T790M mutations who initially received false negative results for the presence of EGFR T790M before hybrid-capture based comprehensive genomic profiling positively identified the presence of the mutation in matched tissue biopsies. The course of therapy before identification of T790M and the subsequent treatments and clinical outcomes are described for each patient. Each case demonstrates missed clinical benefit due to false negative testing for EGFR T790M, and highlights the need for sensitive and accurate detection of targetable genomic alterations in order for patients to potentially benefit from matched targeted therapies. Highlights: EGFR T790M arises in over 50% of EGFR-driven NSCLCs with acquired resistance. Third-generation pyrimidine-based EGFR TKIs targeting T790M have been developed. Osimertinib was recently FDA-approved for T790M-positive NSCLC. We present T790M-positive cases detected by CGP with prior false negative results. Maximum clinical benefit depends on sensitive and accurate detection of T790M.