On June 1, 2016 the US Food and Drug Administration (FDA) approved the first ever blood test to aid clinical decision making for targeted therapies for lung cancer. This blood test, a companion diagnostic called Cobas EGFR Mutation Test v2, allows the detection of mutations in the EGFR (Epidermal Growth Factor Receptor) gene, such as deletions in Exon 19 or substitutions in Exon 20 (such as L858R), which make lung cancers carrying these genomic alterations susceptible to targeting with therapies such as erlotinib, gefinitib or afatinib (classified as tyrosine kinase inhibitors or TKIs). It is currently the only companion diagnostic that is FDA-approved for detecting EGFR gene alterations in DNA derived from blood plasma or tumor tissue.
Today, the FDA approved an expansion of the Cobas EGFR Mutation Test, developed and manufactured by Roche Molecular Systems, to include testing for the T790M mutation in the EGFR gene, that will qualify patients for treatment with the targeted drug, Osimertinib or Tagrisso. This is an important advance, and exciting news for patients as invasive biopsies especially in the disease resistance setting are usually not possible for many patients, either because progression is at a site that is difficult to biopsy or the patient is not well enough to undergo a biopsy. A blood test liquid biopsy provides a non-invasive route to collect information on what is happening in the patient’s body, to influence clinical decision-making on next steps in terms of treatment and disease management.
Approximately 15-20% of non-small cell lung cancer patients harbor alterations in the EGFR gene. Unfortunately most patients whose tumors are driven by these EGFR mutations such as Exon 19 deletions or L858R, initially respond to EGFR-directed therapies, but eventually develop resistance to these targeted therapies in 9-12 months. One of the leading reasons for the emergence of this resistance to these first-line TKIs, is the EGFR T790M mutation that arises in over 65% of patients over time, as their cancers strive to identify ways to continue to grow despite targeted therapy. In November 2015, the US FDA approved a second-generation TKI therapy called Osimertinib or Tagrisso (developed by AstraZeneca) for targeting lung cancers that harbor the EGFR T790M mutation.
Today’s expanded label for the EGFR Cobas liquid biopsy test will allow patients that progress on treatment with Tarceva or other EGFR-directed TKIs to opt for a simple, non-invasive blood test to identify if their tumors harbor the EGFR T790M mutation, and will therefore respond to therapy with Tagrisso. Blood-based testing for the presence of the mutation is recommended only when a tumor biopsy cannot be obtained. Patients who test negative for the EGFR T790M mutation, and their physicians, should re-evaluate the feasibility of tissue-based testing to confirm the presence of the EGFR T790M mutation.
As important advances are being made in the lung cancer therapeutic space, it is heartening to note that advances in the diagnostic space are beginning to keep up. We need more non-invasive, simpler, quicker and relatively painless ways to track cancer’s response to therapy, and the emergence of treatment resistance, so that our cancer treatment plans can always stay a step ahead. To this end, the Addario Lung Cancer Medical Institute, ALCMI, is developing a liquid biopsy study, titled “A Master Protocol to Define the Role of Liquid Biopsies in Small (SCLC) and Non-Small Cell Lung Cancer (NSCLC) Patients”, led by investigators at the Ohio State University, Memorial Cancer Institute, the University of Manchester, among many others. This study will work with several stakeholders in the lung cancer healthcare delivery ecosystem to evaluate the clinical utility and analytically validate liquid-based biomarkers, specifically circulating cell free DNA (cfDNA), RNA, circulating tumor cells (CTCs), and exosomes from blood or urine samples of lung cancer patients taken before, during and after lung cancer therapy and/or surveillance. To learn more about this effort, and how you can participate, email us at [email protected].