Impact of EGFR Mutations on Treatment Decisions in NSCLC

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Anne S. Tsao, MD, David Gandara, MD, Corey A. Langer, MD, Mark A. Socinski, MD, and Alan B. Sandler, MD, discuss the intricacies of treating patients with advanced lung cancer with an EGFR mutation.

When presented with a case study of a 39-year-old non-smoking woman with stage IV adenocarcinoma, Tsao says that she would not offer treatment with erlotinib without the completion of molecular testing. Gandara notes that in the IPASS study, which Tsao referenced, patients did better when receiving chemotherapy in the front-line, if they did not have an EGFR mutation. Langer notes that findings from the IPASS study stressed that even if a patient phenotypically seemed as if they should have an EGFR mutation, testing was still necessary. In the trial, nearly 40% of patients who seemed to have EGFR-positive lung cancer actually tested negative for the mutation.

Sandler agrees, saying that identifying a population that should not be treated with an agent is equally as important as identifying a population that should be treated. In addition to detecting EGFR-negative tumors, Tsao notes, a biopsy may also indicate patients with a T790M mutation, which denotes resistance.

There are common EGFR mutations, Socinski notes, but also many uncommon types of mutations exist as well, which are not well understood. Mutations to exons 19 and 21 are common and occur in approximately 90% of patients. These types of mutations typically respond well to EGFR inhibitors. The other 10% are labeled uncommon and often do not respond as well to treatment. Even with common mutations, Socinski adds, there are differences between mutations in exon 19 and 21.

Langer and Tsao conclude the conversation by stating that uncommon mutations are being studied more frequently. Additionally, Tsao advises physicians that the type of EGFR mutation plays a role in how patients respond to treatment.