Background: Osimertinib is a 3rd-generation, CNS-active, EGFR-TKI with superior efficacy to comparator EGFR-TKI in treatment-naïve EGFRm advanced NSCLC. Approx. 30% of patients with NSCLC present with resectable disease. Adjuvant chemotherapy is standard-of-care in patients with resected stage IIꟷIII NSCLC and select stage IB patients; however, recurrence rates are high. ADAURA (NCT02511106) is a Phase III, double-blind, randomised study assessing efficacy and safety of osimertinib vs placebo in patients with stage IBꟷIIIA EGFRm NSCLC after tumour resection and adjuvant chemotherapy, when indicated. Following Independent Data Monitoring Committee recommendation, the trial was unblinded early due to efficacy; we report an unplanned interim analysis.
Methods Eligible patients: ≥18 years, WHO PS 0/1, primary non-squamous stage IB/II/IIIA NSCLC, confirmed EGFRm (ex19del/L858R), complete resection of primary NSCLC with full recovery from surgery; postoperative chemotherapy was allowed. Patients were randomized 1:1 to osimertinib 80 mg once daily orally or placebo for up to 3 years. Primary endpoint: disease-free survival (DFS) in stage IIꟷIIIA patients. Secondary endpoints: overall survival (OS) and safety. Data cutoff (DCO): 17 Jan 2020.
Results: Globally, 682 patients were randomised to osimertinib (n=339) or placebo (n=343). Baseline characteristics were balanced across arms. In stage IIꟷIIIA patients, DFS hazard ratio (HR) was 0.17 (95% CI 0.12, 0.23); p<0.0001; 2-year DFS rate was 90% with osimertinib vs 44% with placebo. In the overall population, DFS HR was 0.21 (0.16, 0.28); p<0.0001; 2-year DFS rate was 89% with osimertinib vs 53% with placebo. OS was immature (4% maturity) with 29/682 deaths (osimertinib n=9, placebo n=20) at DCO. The safety profile was consistent with that known for osimertinib.
Conclusions: Adjuvant osimertinib showed a statistically significant and clinically meaningful improvement in DFS in patients with stage IB/II/IIIA EGFRm NSCLC after complete tumour resection and adjuvant chemotherapy, when indicated, and provides an effective new treatment strategy for these patients.