Osimertinib for the Treatment of Metastatic EGFR T790M Mutation–Positive Non–Small Cell Lung Cancer

Abstract

On November 13, 2015, the FDA granted accelerated approval to osimertinib (TAGRISSO; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer, as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (FIH; AURA extension; = 201) and a fixed-dose, activity-estimating trial (AURA2; = 210). Osimertinib was administered at 80 mg orally once daily. The objective response rates (ORR) per blinded independent committee review were 57% [95% confidence interval (CI), 50-64) in AURA extension and 61% (95% CI, 54-68) in AURA2. Median duration of response (DOR) could not be estimated. Supportive efficacy data from 63 patients in the dose-finding part of the FIH trial demonstrated an ORR of 51% (95% CI, 38-64), with a median DOR of 12.4 months. Common adverse events (AE) evaluated in 411 patients included diarrhea (42%), rash (41%), dry skin (31%), and nail toxicity (25%). Grade 3 to 4 AEs occurred in 28% of patients, and 5.6% discontinued treatment due to AEs. .

Update review of skin adverse events during treatment of lung cancer and colorectal carcinoma with epidermal growth receptor factor inhibitors

“…Investigator assessed the osimertinib associated adverse events in the AURA Study Phase II Extension Component, showing rash was also predominant (8). Future safety analyses from AURA extension and AURA2 included clustered terms of rash (41%), dry skin (31%), and nail toxicity (25%) (15). The result of AURA3 presented that osimertinib did not share more incidence of skin toxicity than first-generation and second-generation TKI.…”

FDA Approval Summary: Dabrafenib and Trametinib for the Treatment of Metastatic Non-Small Cell Lung Cancers Harboring BRAF V600E Mutations

“…Prior to these approvals, the U.S. Food and Drug Administration (FDA) had not approved any drugs specifically for the treatment of this rare subset of NSCLC. However, demonstration of a large treatment effect on overall response rate (ORR) that is very durable has led to approvals for targeted therapies specifically for the treatment of EGFR T790M‐mutant , ALK rearrangement‐positive , and ROS‐1 ‐mutant NSCLC .…”

The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

“…e most common and famous alteration is EGFR T790M mutation. e efficiency of the third-generation EGFR-TKI osimertinib in treating EGFR T790M mutated patients has been demonstrated in several studies [9][10][11]. However, more targeted and rare mutations and biomarkers are needed to use in clinical practice for prolonging survival of NSCLC patients.…”