Reflex Testing of Resected Stage I Through III Lung Adenocarcinomas for EGFR and KRAS Mutation: Report on Initial Experience and Clinical Utility at a Single Center

Objective: The genes KRAS and EGFR have emerged as potential targets for therapy in lung adenocarcinoma; mutations in these genes can be found in almost half of patients. In anticipation of the clinical importance of molecularly defined adenocarcinoma subgroups for the treatment of patients with resected stages I through III lung adenocarcinoma, the Memorial Sloan-Kettering Cancer Center (MSKCC) Departments of Surgery and Pathology have collaborated since 2006 to conduct reflex testing of tumor specimens for EGFR and KRAS mutations.

Methods: Using established methods, the identification of EGFR exon 19 deletions and exon 21 L858R mutations was performed. In samples lacking these 2 sensitizing EGFR mutations, KRAS analysis was done.

Results: We studied a total of 1831 patients who had stage I through IV lung adenocarcinomas and detected 448 KRAS and 364 EGFR mutations. Of these patients, a subset of 855 (78%) patients with stages I through III adenocarcinoma of the lung who underwent curative surgical resection at MSKCC were tested. In patients with early stage disease, 158 EGFR mutations and 207 KRAS mutations were detected.

Conclusions: The results of the first 3 years of reflex testing at MSKCC reported here demonstrate the feasibility, clinical utility, and potential of this approach. This information allowed for enrollment of patients into clinical trials to explore mutation-specific, directed therapy and led to retrospective studies related to patient outcome. In addition, it may inform selection of chemotherapy for recurrent disease and may help to distinguish multiple primary tumors from metastatic disease.