Testing for EGFR gene mutations in non-small cell lung cancer (NSCLC) helps identify patients who could benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva), gefitinib (Iressa), or afatinib. However, there are no official recommendations for specific EGFR mutation tests. A study comparing three tests—cobas EGFR Mutation Test, Therascreen EGFR29 Mutation Kit, and 2× bidirectional Sanger sequencing—found that the cobas and Therascreen tests were more accurate and sensitive than Sanger sequencing. The cobas test required the smallest amount of tumor tissue, while the Sanger test can theoretically detect more types of mutations than the other tests.
Tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva) and gefitinib (Iressa) are effective treatments for many patients with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene. However, patients who also have a certain version of the BIM gene are resistant to TKIs. Vorinostat (Zolinza), a member of a family of drugs called histone deacetylase (HDAC) inhibitors, restored the antitumor activity of Iressa in EGFR-mutant NSCLC cells and in animal models of EGFR-mutant NSCLC that carried the resistant BIM version. Combining Zolinza with TKIs may therefore help circumvent TKI resistance in patients who have the resistant form of BIM.
Non-small cell lung cancer (NSCLC) patients with mutations in the EGFR gene are likely to benefit from treatment with tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva) and gefitinib (Iressa), while KRAS mutations predict poor TKI response. A study of patients who were not taking TKIs and had stages I/II/III NSCLC that had been surgically removed found no difference in recurrence or survival between patients with or without EGFR or KRAS mutations. This finding suggests that, while EGFR and KRAS mutations are useful for identifying patients who may benefit from targeted treatments like TKIs, they do not predict overall clinical outcomes by themselves.
Three percent to 5% of non-small cell lung cancer (NSCLC) patients have a mutation in the ALK gene and may benefit from treatment with critozinib (Xalkori). In 2011, the FDA approved a test that samples NSCLC tissue and highlights ALK mutations with a glowing tag. Now, the FDA has approved an automated scanning system, GenASIs Scan & Analysis, for examining these tagged tissue samples. The automated system, produced by Applied Spectral Imaging, promises fast, reliable detection of ALK mutations in NSCLC.
An analysis of multiple clinical trials compared erlotinib (Tarceva) alone to combining Tarceva with other targeted therapies as second-line treatment for advanced non-small cell lung cancer (NSCLC). In the various trials, Tarceva was combined with bevacizumab (Avastin), bortezomib (Velcade), everolismus (Afinitor), sorafenib (Nexavar), sunitinib (Sutent), entinostat, tivantinib, and R1507. While combined therapy produced more side effects, it was more effective than Tarceva alone. Notably, the trials included many patients who had not been tested for mutations in the EGFR and KRAS genes. In patients who had EGFR mutations and/or lacked KRAS mutations, Tarceva alone tended to control cancer progression better than combined therapy, highlighting the importance of biomarker testing to identify which patients are most likely to benefit from different therapies.