Purpose: Reliable detection of drug sensitive activating EGFR mutations is critical in the care of advanced non-small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation. Experimental Design: A large pool of NSCLC cases was assayed with well validated, hybrid-capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. From these, 400 cases harboring EGFR exon 19 deletions (∆ex19) were identified and available clinical history was reviewed. Results: Pathology reports were available for 250 consecutive cases with classical EGFR ∆ex19 (amino acids 743-754), and reviewed to assess previous non-hybrid capture based EGFR testing. Twelve of 71 (17%) cases with EGFR testing results available were negative by previous testing, including 8/46 (17%) cases for which the same biopsy was analyzed. Independently, 5 of 6 (83%) cases harboring C-helical EGFR ∆ex19 were previously negative. In a subset of these patients with available clinical outcome information, robust benefit from treatment with EGFR inhibitors was observed. Conclusions and Relevance: CGP identifies drug sensitive EGFR ∆ex19 in NSCLC cases which have undergone prior EGFR testing and returned negative results. Given the proven benefit in progression free survival conferred by EGFR tyrosine kinase inhibitors in patients with these alterations, CGP should be considered in the initial presentation of advanced NSCLC and when previous testing for EGFR mutations or other driver alterations is negative.
- Received July 14, 2015.
- Revision received January 3, 2016.
- Accepted January 23, 2016.
- ©2015 American Association for Cancer Research.