Background
Genomic testing to identify driver mutations that enable targeted therapy is emerging for patients with non-small cell lung cancer (NSCLC). We report the implementation of systematic prospective genotyping for somatic alterations in BRAF, PIK3CA, HER2, and ALK, in addition to EGFR and KRAS, in NSCLC patients at the Dana-Farber Cancer Institute.
Methods
Patients with NSCLC were prospectively referred by their providers for clinical genotyping. Formalin-fixed, paraffin embedded tumor samples were analyzed by Sanger sequencing for mutations in selected exons of EGFR, KRAS, BRAF, PIK3CA, and HER2. ALK rearrangements were detected by FISH or immunohistochemistry.
Results
Between 7/1/2009 and 8/1/2010, 427 specimens from 419 patients were referred for genomic characterization; 344 (81%) specimens were successfully genotyped with a median turnaround time of 31 days (range, 9-155). Of the 344 specimens, 185 (54%) had at least one identifiable somatic alteration (KRAS: 24%, EGFR: 17%, ALK: 5%, BRAF: 5%, HER2: 4%, PIK3CA: 2%). As of 8/1/2011, 63/288 (22%) advanced NSCLC patients had received molecularly targeted therapy based on their genotypic results, including 34/42 (81%) patients with EGFR mutations, 12/15 (80%) with ALK rearrangements, and 17/95 (18%) with KRAS, BRAF or HER2 mutations.
Conclusions
Large scale testing for somatic alterations in EGFR, KRAS, BRAF, PIK3CA, HER2 and ALK is feasible and impacts therapeutic decisions. As the repertoire for personalized therapies expands in lung cancer and other malignancies, there is a need to develop new genomics technologies that can generate a comprehensive genetic profile of tumor specimens in a time and cost effective manner.