The U.S. Food and Drug Administration granted regular approval to Tagrisso (osimertinib) for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.
Lung cancer remains the leading cause of cancer-related deaths in the United States. Non-small cell lung cancer is the most common type of lung cancer, according to the type of cell within the lung from which the cancer originated.
As personalized precision medicine treatment approaches continue to gain momentum in the treatment of cancer, several specific gene mutations have been identified that contribute to the growth and spread of certain cancers. Once these mutations are identified, researchers attempt to develop agents that specifically target the effects caused by the mutations.
EGFR is a type of protein that is found on the surface of many cells. It is part of a pathway involved in normal cellular growth. However, mutations within the EGFR gene can result in the production of too many EGFR proteins, and can result in unregulated spread of cancer cells.
Standard treatment for patients who have too many EGFR proteins, referred to as EGFR+ cancer, includes EGFR tyrosine kinase inhibitors (EGFR TKIs). These drugs block the growth stimulatory effects of the mutations within the EGFR pathway, and reduce the spread of cancer.
Although EGFR TKIs are an effective treatment option for patients with EGFR+ NSCLC, the cancer stops responding to these agents after approximately 9-13 months of treatment. Often, the cancers will develop additional mutations that allow that cancer cells to begin growing again, despite treatment with EGFR TKIs. One such common mutation that can develop during EGFR TKI therapy is the T790 mutation (T790M).
Tagrisso is a targeted agent that blocks the effects of T790M. It is already approved by the United States Food and Drug Administration (FDA) for the treatment of advanced EGFR+ NSCLC that has stopped responding to EGFR TKI therapy, and has the T790M.
The current approval of Tagrisso is based on a comparative clinical trial, conducted in patients with metastatic EGFR T790M mutation-positive NSCLC who had progressive disease following first-line EGFR TKI therapy. Patients were treated with Tagrisso or a standard platinum based chemotherapy regimen.
Overall 65% of Tagrisso treated patients responded to treatment compared to only 29% of those receiving platinum. Tagrisso treated patients survived without cancer progression almost 2.5 times longer than those treated with platinum chemotherapy. In patients with central nervous system (CNS) lesions on baseline brain scans, the 57% of Tagrisso treated patients experienced a response.
The most common side effects of treatment were diarrhea, rash, dry skin, nail toxicity, and fatigue. The FDA notes that the presence of an EGFR T790M mutation in a tumor specimen, or plasma specimen (if tumor tissue is unavailable) should be confirmed by an FDA-approved test prior to initiation of treatment.