On November 13, 2015, the U. S. Food and Drug Administration granted accelerated approval to osimertinib (TAGRISSO) once daily tablets, AstraZeneca Pharmaceuticals LP, 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, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.
The approval was based on two multicenter, single-arm, open-label clinical trials in patients with metastatic EGFR T790M mutation-positive NSCLC who had progressed on prior systemic therapy, including an EGFR TKI (Study 1 and 2).  All patients were required to have EGFR T790M mutation-positive NSCLC as detected by the cobas® EGFR mutation test and received osimertinib 80 mg once daily. The major efficacy outcome measure was objective response rate (ORR) according to RECIST v1.1 as evaluated by a Blinded Independent Central Review (BICR). Duration of response (DOR) was an additional outcome measure.
Study 1 (n=201) showed an ORR of 57% (95% CI: 50%, 64%). In Study 2 (n=210) the ORR was 61% (95% CI: 54%, 68%). The majority (96%) of patients in both trials had ongoing responses at the time of primary analysis and the median DOR had not been reached with duration of ongoing responses ranging from 1.1 to 5.6 months after a median duration of follow-up of 4.2 months (Study 1) and 4.0 months (Study 2).  The dose finding phase of Study 1 (n=63) showed an ORR of 51% and median DOR of 12.4 months.  
Safety data was evaluated in 411 patients who received osimertinib at a dose of 80 mg daily. The most common adverse events were diarrhea (42%), rash (41%), dry skin (31%), nail toxicity (25%), eye disorders (18%), nausea (17%), decreased appetite (16%), and constipation (15%).  The majority of the above adverse events were grade 1-2. The most common Grade 3-4 adverse reactions were pneumonia and pulmonary embolism (2% each).
The most common nonfatal serious adverse events (SAEs) included pneumonia and pulmonary embolus. Dose reductions due to adverse events occurred in 4.4% of patients. The most frequent adverse reaction leading to dose reductions or interruptions were prolonged QTc and neutropenia (2% each). Adverse events leading to discontinuation included ILD/pneumonitis (2%), and cerebrovascular accident (1%).  Fatal adverse events occurred in 3.2% of patients, including 4 cases of pneumonitis attributed to osimertinib.
The recommended dose and schedule for osimertinib is 80 mg given orally once daily. 
Osimertinib received Breakthrough Therapy Designation and the current indication was approved under FDA’s accelerated approval program. The application was granted a Priority Review. This application was approved before the Prescription Drug User Fee Act (PDUFA) goal date of February 6, 2016.  A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.
Full prescribing information is available at: 
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Page Last Updated: 11/13/2015
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