Frontline Osimertinib Extends PFS in EGFR+ NSCLC

Frontline osimertinib (Tagrisso) significantly improved progression-free survival versus standard of care in patients with locally-advanced or metastatic EGFR-positive non–small cell lung cancer.

Sean Bohen, MD, PhD

Frontline osimertinib (Tagrisso) significantly improved progression-free survival (PFS) versus standard of care in patients with locally-advanced or metastatic EGFR-positive non—small cell lung cancer (NSCLC), according to results from the phase III FLAURA trial.

AstraZeneca, the manufacturer of the EGFR inhibitor, announced the findings today in a press release, but did not release any details on the outcomes. The company reported that osimertinib showed a statistically-significant and clinically-meaningful PFS benefit compared with erlotinib (Tarceva) or gefitinib (Iressa) in treatment-naïve patients.

“The strong results from the FLAURA trial are very exciting news for patients with EGFR mutation-positive non—small cell lung cancer, providing physicians with a potential new first-line treatment option to improve outcomes in this disease,” Sean Bohen, MD, PhD, AstraZeneca’s chief medical officer, said in a statement. “We will now initiate discussions with global health authorities on the data and regulatory submissions.”

In the double-blind trial, treatment-naïve patients with EGFR-positive locally advanced or metastatic NSCLC were randomly assigned to osimertinib (80 mg or 40 mg orally once daily), or standard of care with erlotinib (150 mg once daily) or gefitinib (250 mg once daily). Researchers recruited 556 patients across 30 countries.

Osimertinib is a third-generation, irreversible EGFR tyrosine kinase inhibitor (TKI) designed to inhibit both EGFR sensitizing and EGFR T790M resistance mutations, with clinical activity against CNS metastases.

Investigators are still analyzing the data from FLAURA and plan to release further details at a future medical meeting.

First-line treatment with single-agent osimertinib was associated with a 77% response rate in treatment-naïve patients, according to phase I data presented at the 2016 European Lung Cancer Conference (ELCC).1 The findings came from a study comprising 60 patients with locally advanced or metastatic EGFR+ NSCLC from 2 phase I expansion cohorts of the phase I/II AURA trial.

At median follow-up of 16.6 months, the overall response rate (ORR) was 67% (95% CI, 47-83) for patients assigned to 80 mg once daily osimertinib and 87% (95% CI, 69-96) for patients assigned to 160 mg groups. The overall disease control rate (complete response + partial response + stable disease) was 97% (95% CI, 88.5-99.6), including 93% (95% CI, 78-99) and 100% (95% CI, 88-100) in the 80- and 160-mg cohorts, respectively.

Overall, 72% of patients were alive and progression-free at 12 months, including 75% of patients in the 80-mg arm and 69% of patients in the 160-mg arm. More than half of patients (55%) were progression-free at 18 months, including 57% in the 80-mg arm and 53% in the 160-mg arm.

The most common all-grade adverse events (AEs) were rash (70% with 80 mg; 87% with 160 mg), diarrhea (60%, 87%), dry skin (57%, 60%), stomatitis (43%, 50%), and paronychia (37%, 63%). Grade ≥3 AEs for the 160-mg arm included diarrhea (7%), paronychia (7%), rash (3%), and stomatitis (3%). One patient in the 80 mg-arm had grade ≥3 nausea.

The FDA granted osimertinib a full approval for patients with metastatic EGFR T790M mutation-positive NSCLC following prior treatment with an EGFR TKI in March of this year.2 The full approval followed an accelerated approval granted in November 2015.

The full approval was based on the randomized phase III AURA3 trial, in which osimertinib had a median PFS of 10.1 months compared with 4.4 months for standard platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41; P <.001).

Median PFS for patients with CNS metastases was 8.5 months with osimertinib versus 4.2 months with chemotherapy (HR, 0.32; 95% CI, 0.21-0.49).

The ORR with osimertinib was 71% versus 31% with chemotherapy (odds ratio, 5.39; 95% CI, 3.47-8.48; P <.001). The 6-month PFS rate was 69% with osimertinib versus 37% with chemotherapy. At 12 months, 44% of those in the osimertinib arm were progression-free versus 10% in the chemotherapy group.

Grade ≥3 AEs were reported in 23% of the osimertinib group versus 47% of the chemotherapy arm. The most frequently reported grade ≥3 events in the chemotherapy arm were neutropenia (12%), anemia (12%), and thrombocytopenia (7%). The incidence of each of those toxicities in the osimertinib arm was 1% or less.


  1. Ramalingam S, Yang JC, Lee CK, et al. Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two phase I expansion cohorts. Presented at: 2016 European Lung Cancer Conference; April 13-16, 2016; Geneva, Switzerland. Abstract LBA 1.
  2. Mok TS, Wu YL, Ahn MJ, et al. The AURA3 Investigators. Osimertinib or platinum—pemetrexed in EGFR T790M–positive lung cancer. N Engl J Med. 2017; 376:629-640.