Osimertinib targets oncogenic mutant forms of EGFR, including those harbouring the T790M mutation that is commonly responsible for the development of resistance to other EGFR inhibitors. The T790M mutation is found in nearly two-thirds of NSCLC patients who experience disease progression after treatment with the EGFR inhibitors gefitinib, erlotinib or afatinib.
The safety and efficacy of osimertinib were demonstrated in two open-label single-arm studies involving a total of 411 patients with advanced EGFR T790M mutation-positive NSCLC whose disease had progressed after treatment with an EGFR inhibitor.
In total, 61% of patients in the first study (AURAex) and 71% of patients in the second study (AURA2) experienced a complete or partial reduction in their tumour size. Responses lasted a median of 7.8 months in AURA2, with a median progression-free survival of 8.6 months (these endpoints were not evaluable for AURAex).
Interstitial lung disease
The most commonly reported adverse reactions to osimertinib were diarrhoea (42%) and rash (24%). Interstitial lung disease occurred in 2.9% of patients and should be excluded in individuals presenting with acute onset and/or unexplained worsening of pulmonary symptoms such as dyspnoea or cough.
Osimertinib is also associated with QT prolongation. Use of the drug should be avoided in patients with congenital long QT syndrome; periodic ECG and electrolyte monitoring should be conducted in patients with congestive heart failure, electrolyte abnormalities, and those who are taking other agents that prolong the QT interval.
Tagrisso is the first new medicine to be approved under the European Commission's expedited process and authorisation is conditional on further evidence of clinical benefit.