Osimertinib Granted European Approval for Frontline Treatment of EGFR-mutant NSCLC

Osimertinib (Tagrisso) has been approved by The European Commission as a frontline treatment for patients with&nbsp;<em>EGFR</em>-mutant locally-advanced or metastatic non&ndash;small cell lung cancer. The approval is based on data&nbsp;from the phase III FLAURA trial.

David Planchard MD, PhD

Osimertinib (Tagrisso) has been approved by The European Commission as a frontline treatment for patients withEGFR-mutant locally-advanced or metastatic non—small cell lung cancer (NSCLC). The approval is based on data from the phase III FLAURA trial.

In the double-blind study, which was published in theNew England Journal of Medicine,frontline osimertinib reduced the risk of progression or death by 54% versus erlotinib (Tarceva) or gefitinib (Iressa). The median progression-free survival (PFS) was 10.2 months (95% CI, 9.6-11.1) for standard TKI therapy and 18.9 months (95% CI, 15.2-21.4) with osimertinib (HR, 0.46; 95% CI, 0.37-0.57;P<.0001).

“The FLAURA trial is changing medical practice in the first-line treatment ofEGFR-mutated NSCLC," David Planchard, MD, PhD, associate professor of Medicine, Head of Thoracic Group, Gustave Roussy Cancer Center, said in a statement. "The progression-free survival benefit seen in the trial is unprecedented for patients with anEGFRmutation, and this benefit was consistent across all subgroups including in patients with or without central nervous system metastases."

At the early interim analysis, 25% of anticipated events had occurred for overall survival. Although not yet statistically significant, there was an early 37% reduction in the risk of death with osimertinib versus standard TKI (HR, 0.63; 95% CI, 0.45-0.88; P = .0068).

"The preliminary overall survival data, while not statistically significant at the time of the interim analysis, is promising, with a 37% reduction in the risk of death," said Planchard.

In the FLAURA trial, 556 treatment-naïve patients withEGFR-positive locally advanced or metastatic NSCLC were randomly assigned to osimertinib (n = 279) or a standard TKI (erlotinib or gefitinib; n = 277). Patients with CNS metastases were allowed on the trial and all patients had exon 19 deletions or L858R mutations. Daily oral therapy was given with 80 mg of osimertinib, 250 mg of gefitinib, or 150 mg of erlotinib.

The objective response rate with osimertinib was 80% compared with 76% for erlotinib and gefitinib (odds ratio 1.28, 95% CI, 0.85-1.93;P= .2335). The median duration of response with osimertinib was 17.2 months versus 8.5 months in the comparator arm.

In patients with CNS metastases (n = 116), the median PFS with osimertinib was 15.2 months (95% CI, 12.1-24.4) compared with 9.6 months (95% CI, 7.0-12.4) with standard therapy (HR, 0.47; 95% CI, 0.30-0.74;P= .0009). In those without CNS involvement (n = 440), the median PFS was 19.1 months (95% CI, 15.2-23.5) and 10.9 months (95% CI, 9.6-12.3), for osimertinib and the control arm, respectively (HR, 0.46; 95% CI, 0.36-0.59;P<.0001). Across all patients, CNS progression occurred in 6% treated with osimertinib versus 15% for erlotinib and gefitinib.

The most common all-grade adverse events (AEs) were diarrhea (58%) and dry skin (32%) in the experimental group compared with diarrhea (57%) and dermatitis acneiform (48%) in the control group. Overall, 33.7% of patients experienced a grade ≥3 AE in the osimertinib group compared with 44.8% for erlotinib and gefitinib. Patients in the osimertinib group were less likely to discontinue treatment because of AEs (13.3% vs 18.1%).

“Today’s approval is an exciting advance in bringing a potential new standard of care to patients withEGFR-mutated NSCLC in the European Union [EU]," Dave Fredrickson, executive vice president, Head of the Oncology Business Unit at AstraZeneca, the company developing osimertinib, said in a statement. "This milestone is also a step forward for our Company, marking another regional approval for Tagrisso in the first-line setting.”

Osimertinib was initially granted an accelerated approval by the FDA in November 2015 and was approved in the EU in February 2016 under an expedited process for pretreated patients withEGFRT790M-positive NSCLC. Findings from the phase III AURA3 trial subsequently validated these approvals, which were based on early phase clinical trials.


Soria J-C, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non—Small-Cell Lung Cancer.N Engl J Med.2018;378:113-125.