FDA Grants Osimertinib Full Approval in Metastatic EGFR T790M Mutation–Positive NSCLC
On March 30, 2017, the U.S. Food and Drug Administration (FDA) granted regular approval to osimertinib (Tagrisso) 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 therapy.
In November 2015, osimertinib received accelerated approval for this indication based on an overall response rate of 59% among 411 patients in two single-arm clinical trials.
AURA3 Trial
The current approval is based on AURA3, a randomized, multicenter open-label, active-controlled trial conducted in patients with metastatic EGFR T790M mutation–positive NSCLC who had progressive disease following first-line EGFR tyrosine kinase inhibitor therapy. All patients were required to have EGFR T790M mutation–positive NSCLC identified by the cobas EGFR mutation test performed in a central laboratory.
AURA3 randomized 419 patients (2:1) to receive osimertinib (n = 279) 80 mg orally once daily or platinum-based doublet chemotherapy (n = 140). Patients in the chemotherapy arm received either pemetrexed 500 mg/m2 with carboplatin AUC5, or pemetrexed 500 mg/m2 with cisplatin 75 mg/m2), on day 1 of every 21-day cycle for up to six cycles followed by pemetrexed maintenance therapy. Patients on the chemotherapy arm with radiologic progression according to both investigator and blinded independent central review were offered osimertinib at progression.
AURA3 demonstrated an improvement in investigator-assessed progression-free survival, with a hazard ratio of 0.30 (95% confidence interval [CI] = 0.23–0.41; P < .001). The estimated median progression-free survival was 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm. Confirmed overall response rate, according to investigator assessment, was 65% (95% CI = 59%–70%) and 29% (95% CI = 21%–37%) in the osimertinib and chemotherapy arms, respectively (P < .0001). Estimated median response durations were 11 months (95% CI = 8.6–12.6) and 4.2 months (95% CI = 3.9–5.9) in the osimertinib and chemotherapy arms, respectively.
In patients with measurable central nervous system (CNS) lesions on baseline brain scans, the confirmed CNS overall response rate, assessed by independent central review, was 57% (95% CI = 37%–75%) and 25% (95% CI = 7%–52%) in the osimertinib and chemotherapy arms, respectively. The median CNS response duration was not reached in the osimertinib arm (range, 1.4–12.5 months) and was 5.7 months (range, 1.4–5.7 months) in the chemotherapy arm. Overall survival data are immature.
Serious adverse reactions were evaluated in 833 patients receiving osimertinib. The most serious adverse reactions were interstitial lung disease/pneumonitis (3.5%), QTc interval prolongation (0.7%), cardiomyopathy (1.9%), and keratitis (0.7%). The most common adverse reactions (occurring in at least 20% of patients) were diarrhea, rash, dry skin, nail toxicity, and fatigue.
The recommended dose of osimertinib is 80 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. 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.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
