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The FDA has granted full approval for osimertinib 80 mg once-daily tablets 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 an EGFR tyrosine kinase inhibitor (TKI) therapy. Osimertinib is the first and only approved medicine in the U.S. indicated for NSCLC patients who have tested positive for the EGFR T790M mutation, and efficacy data suggest it may be a new standard of care for these patients.

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The full approval in the U.S. is based on data from the randomized, phase III AURA3 trial, in which osimertinib significantly improved progression-free survival (PFS) versus platinum-based doublet chemotherapy, providing 10.1 months of median PFS compared to 4.4 months from chemotherapy (hazard ratio 0.30; 70% risk reduction; 95% confidence interval [CI]: 0.23; 0.41; P<0.001).


Additionally, in a post-hoc subgroup analysis of patients with measurable central nervous system (CNS) lesions, osimertinib demonstrated an objective response rate (ORR) of 57 percent (95% CI: 37%; 75%) compared to 25 percent ORR from chemotherapy (95% CI: 7%; 52%). For CNS patients receiving osimertinib, median duration of response, defined as the time from the date of first documented response until progression or death event, was not yet reached at the time of analysis. CNS metastases are typically difficult to treat, carry a very poor prognosis, and affect up to 40 percent of patients with NSCLC.


In AURA3, the most common (>20%) adverse reactions observed in osimertinib-treated patients were diarrhea (41%), rash (34%), dry skin (23%), nail toxicity (22%), and fatigue (22%). Dose reductions occurred in 2.9 percent of patients treated with osimertinib. The most frequent adverse reactions that led to dose reductions or interruptions were prolongation of the QT interval as assessed by ECG (1.8%), neutropenia (1.1%), and diarrhea (1.1%). Serious adverse reactions were reported in 18 percent of patients treated with osimertinib and 26 percent of patients in the chemotherapy group. No single serious adverse reaction was reported in 2 percent or more patients treated with osimertinib.


"While most lung cancer specialists have already been very impressed with their earlier experience with osimertinib and embraced the opportunity to use it for T790M mutation-positive patients with acquired resistance to EGFR-TKI therapy, AURA3 provides even more compelling evidence," noted H. Jack West, MD, Medical Oncology, Medical Director, Thoracic Oncology Program, Swedish Cancer Institute. "Here, we saw a striking efficacy benefit in favor of osimertinib over chemotherapy in T790M mutation-positive patients. Testing for EGFR T790M should be a critical next step in patients who develop acquired resistance after first-line EGFR TKI therapy."


Osimertinib was granted Fast Track, Breakthrough Therapy, and Priority Review designations by the FDA, and received Accelerated Approval for this indication in 2015 based on tumor response rate and duration of response. In September 2016, the FDA approved a blood-based companion diagnostic, representing the only FDA-approved and clinically-validated companion diagnostic test that uses a blood sample to confirm the presence of a T790M mutation. Blood-based testing is recommended only when a tumor biopsy cannot be obtained; if a patient tests negative for the T790M mutation with the blood-based test, their physician should re-evaluate the feasibility of tissue-based testing.