Adjuvant Osimertinib Succeeds in Phase III ADAURA Trial in EGFR+ NSCLC

The phase III ADAURA trial of adjuvant osimertinib in patients with EGFR mutation–positive non–small cell lung cancer has been unblinded due to “overwhelming efficacy.”

José Baselga, MD, PhD

Due to the “overwhelming efficacy” demonstrated by adjuvant osimertinib (Tagrisso) in the treatment of patients with stage Ib, II and IIIa EGFR mutation—positive non–small cell lung cancer (NSCLC) with complete tumor resection, the phase III ADAURA trial will be unblinded early, according to AstraZeneca, the manufacturer of the third-generation EGFR TKI.1

In the study, adjuvant osimertinib was compared with placebo for a treatment period of up to 3 years. The primary endpoint was disease-free survival, and the study is continuing to evaluate overall survival (OS), a secondary endpoint. The data readout was originally supposed to occur in 2022. No new safety issues were communicated by the Independent Data Monitoring Committee when it recommended the unblinding. AstraZeneca plans to share the study data at a future medical meeting.

"We are thrilled by the recommendation to unblind the phase III ADAURA trial much earlier than expected and are incredibly excited with these unprecedented results in patients with early-stage EGFR-mutated non—small cell lung cancer. Lung cancer is a devastating diagnosis and for the first time an EGFR-targeted medicine can now provide the hope of cure,” José Baselga, executive vice president, Oncology R&D, AstraZeneca, stated in a press release.

The global, double-blinded, randomized phase III ADAURA trial evaluated 682 patients with stage Ib, II, IIIa EGFR—mutant NSCLC with complete tumor resection and optional, standard post-operative adjuvant chemotherapy. Patients were randomized to osimertinib at 80 mg orally once daily or placebo for 3 years or until disease recurrence. Patients were treated at more than 20 countries at more than 200 clinical sites.

In April 2018, the FDA approved osimertinib as a frontline treatment for patients with EGFR-mutant NSCLC, based on findings from the phase III FLAURA trial. Prior to the frontline approval, osimertinib was also granted approval for use following progression on a first- or second-generation TKI, for patients with EGFR T790M—positive NSCLC.

Data from the FLAURA trial presented at the 2019 ESMO Congress showed that frontline treatment with osimertinib improved median OS by 6.8 months compared with erlotinib (Tarceva) or gefitinib (Iressa) for patients with metastatic, EGFR-mutant NSCLC, despite crossover between arms.2

The median OS in the osimertinib arm was 38.6 months (95% CI, 34.5-41.8) compared with 31.8 months (95% CI, 26.6-36.0) with erlotinib or gefitinib, representing a 20% reduction in the risk of death with the third-generation EGFR inhibitor (HR, 0.799; 95% CI, 0.647-0.997; P = .0462). At the final data cutoff for the study, 54% of patients remained alive at 36 months in the osimertinib arm compared with 44% in the erlotinib/gefitinib group.

In the FLAURA trial, 556 treatment-naïve patients with EGFR-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 12-month OS rate was 89% in the osimertinib arm compared with 83% in the comparator group. The 24-month OS rates were 74% and 59%, for osimertinib and erlotinib/gefitinib, respectively. At 36 months, 28% of patients remained on first-line treatment with osimertinib compared with 9% remaining on erlotinib or gefitinib.

In findings from the study published in the New England Journal of Medicine3 prior to the ESMO meeting, the median progression-free survival with osimertinib was 18.9 months (95% CI, 15.2-21.4) versus 10.2 months (95% CI, 9.6-11.1) for erlotinib or gefitinib (HR, 0.46; 95% CI, 0.37-0.57; P <.0001), which was a 54% reduction in the risk of progression or death. The objective response rate with osimertinib was 80% compared with 76% for erlotinib or gefitinib (odds ratio, 1.27; 95% CI, 0.85-1.90; P = .24). The median duration of response with osimertinib was 17.2 months versus 8.5 months in the comparator arm.

Osimertinib also showed better tolerability than the first-generation TKIs. Grade 3/4 adverse events (AEs) occurred in 34% of patients in the osimertinib group compared with 45% of those receiving erlotinib or gefitinib.

The most common all-grade AEs with osimertinib and first-generation TKIs, respectively, were rash or acne (58% vs 78%), diarrhea (58% vs 57%), dry skin (36% vs 36%), paronychia (35% vs 33%), stomatitis (29% vs 20%), and decreased appetite (20% vs 19%). AEs were less likely to lead to treatment discontinuation in the osimertinib arm (13% vs 18% discontinuation rate, respectively).


  1. Tagrisso Phase III ADAURA trial will be unblinded early after overwhelming efficacy in the adjuvant treatment of patients with EGFR-mutated lung cancer. Published April 13, 2020. Accessed April 13, 2020.
  2. Ramalingam SS, Gray JE, Ohe Y, et al. Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis. Presented at: 2019 ESMO Congress, Barcelona, Spain, September 28 to October 1, 2019. Abstract LBA5_PR.
  3. 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.