The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

With no FDA-approved "companion" diagnostic test on the market, CLIA-licensed laboratories developed and validated LDP tests for the 2 most common EGFR mutations as early as 2004. 73 The FDA followed with approval of the Roche Cobas EGFR Mutation Test in 2013 along with the Qiagen therascreen EGFR RGQ Kit. Both assays tested for the exon 19 deletions and the exon 20 L858R point mutation. Of note was that each test was approved for specific therapeutic indications and specimen types. As new drugs became available, approval for new claims was needed. Laboratory-developed procedures continue to be the method of choice due to the limitations of claims made for FDA-approved assays and performance characteristics, including types of mutations being detected. 76 Clinical laboratories participate in twice-yearly proficiency test challenges of unknown samples that must be analyzed and reported, with results graded and compared to other laboratories performing the testing. In the CAP EGFR-B-2015 proficiency test, 192 laboratories reported results from testing 3 unknown proficiency-testing specimens in late 2015. The specimens con- Note: Some laboratories do not test for certain mutations, hence, the denominator is often less than 192. 77 As patients being treated with these new targeted anti-EGFR therapies began to relapse, further studies revealed that EGFR harbors both sensitizing and resistance mutations. The CLIA laboratories have demonstrated the ability to detect all mutations in the EGFR gene as well as in other genes using NGS assays to sequence panels of cancer-related genes. 78 This panel approach allows the laboratory to provide the oncologist with a more comprehensive profile of the tumor, using a costeffective technology that makes maximal use of small tissue samples and thus makes treatment strategies more effective. In addition, the time saved by testing a broader panel of gene targets can result in better outcomes for the patient as well as fewer adverse drug reactions. For the payer, the cost savings of such an approach versus algorithm-based testing with single gene assays is significant. Currently, there are no FDAapproved sequencing assays for EGFR mutation status, and LDPs are solely used for the detection of these mutations that define therapy selection.