A Precision Medicine for Lung Cancer

The FDA-approved therapeutic is the first to target the T790M EGFR mutation that frequently causes resistance to other EGFR-targeted therapeutics

The U.S. Food and Drug Administration (FDA) has approved EGFR-targeted therapeutic osimertinib (Tagrisso), a precision medicine for patients with non-small cell lung cancer (NSCLC) that has a T790M mutation in the EGFR gene and whose disease has progressed despite treatment with other EGFR-targeted therapeutics.

The FDA simultaneously approved a companion diagnostic test to identify the patients whose tumors have the T790M EGFR mutation. The test is called cobas EGFR Mutation Test v2.

About 10 to 15 percent of patients with NSCLC, which is the most commonly diagnosed form of lung cancer in the United States, have tumors that are fueled by mutations in the EGFR gene. According to a review article published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR), although most NSCLCs respond to EGFR-targeted therapeutics such as afatinib (Gilotrif), erlotinib (Tarceva), and gefitinib (Iressa), many become resistant to these treatments after about 9 to 12 months. The most frequent cause of resistance is the acquisition of an EGFR T790M mutation.

Osimertinib, which was previously known as AZD9291, is a precision cancer medicine that specifically targets cancer-driving mutant forms of EGFR, including that produced by the EGFR T790M mutation. Before its approval, the options for physicians treating patients with NSCLC harboring this mutation were extremely limited.

According to the FDA announcement, the decision to approve osimertinib was based on objective response rates from two single-arm phase II clinical trials involving a total of 411 patients with advanced, EGFR T790M mutation?positive NSCLC that had progressed after treatment with another EGFR-targeted therapeutic. In the first study, 57 percent of the 201 patients had a complete or partial reduction in the size of their tumor – that is to say 57 percent had an objective response ? and in the second study, 61 percent of the 210 patients had an objective response.

Because this approval is based on objective response rate data, rather than overall survival, osimertinib’s manufacturer, AstraZeneca, is required by the FDA to conduct a study to confirm that the drug improves survival for patients. A phase III clinical trial to evaluate this was recently opened and the results are keenly awaited.

Osimertinib is also being tested in a number of other ongoing clinical trials. Early results from one of these, which showed that osimertinib crossed the blood-brain barrier and had clinical activity in heavily pretreated non-small cell lung cancer (NSCLC) patients with leptomeningeal disease, were recently presented by Dae Ho Lee, MD, PhD, at the 2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

According to Lee, although these results are very preliminary, they are encouraging given that patients who develop leptomeningeal disease—a disease in which lung cancer cells spread to the membranes surrounding the brain and spinal cord—have very few treatment options and survive only an average of seven to 11 months.

The FDA approval was rendered on Oct. 2, 2015.