The Introduction of Systematic Genomic Testing for Patients with Non–Small-Cell Lung Cancer

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 fluorescence in situ hybridization or immunohistochemistry. Results: Between July 1, 2009 and August 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 August 1, 2011, 63 of 288 advanced NSCLC patients (22%) had received molecularly targeted therapy based on their genotypic results, including 34 of 42 patients (81%) with EGFR mutations, 12 of 15 (80%) with ALK rearrangements, and 17 of 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.