Osimertinib is a third-generation, central nervous system–active, EGFR-targeting tyrosine kinase inhibitor (TKI) with superior efficacy to other TKIs, including gefitinib and erlotinib, in treatment-naïve patients with EGFR-mutated advanced non–small-cell lung cancer (NSCLC). Adjuvant chemotherapy is standard of care in patients with resected stage II to stage III NSCLC and select stage IB patients, but recurrence rates are high. ADAURA is a phase 3, double-blind, randomized study assessing the efficacy and safety of osimertinib versus placebo in patients with stage IB to stage IIIA EGFR-mutated NSCLC after complete tumor resection and adjuvant chemotherapy, when indicated. Following independent data monitoring committee recommendations, the trial was unblinded early due to efficacy. This report summarizes an unplanned interim data analysis.
Eligible patients had to be ≥18 years (≥20 years in Japan and Taiwan); have a performance status of 0 or 1; primary nonsquamous stage IB, II, or IIIA NSCLC; confirmed EGFR mutation (either ex19del or L858R); and 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 and received treatment for up to 3 years. Patients were stratified by disease stage (IB, II, IIIA), mutation type (ex19del, L858R), and race (Asian, non-Asian). The primary end point of the study was disease-free survival (DFS) by investigator in stage II to IIIA patients. Secondary end points were overall survival (OS) and safety. The data cutoff was January 17, 2020.
In total, 682 patients were randomized to treatment: 339 to osimertinib and 343 to placebo. Baseline characteristics were balanced between arms: stage IB 31%/31% (osimertinib/placebo), stage II/IIIA 69%/69%, female 68%/72%, ex19del 55%/56%, and L858R 45%/44%.
In stage II and stage IIA patients, the DFS hazard ratio (HR) was 0.17 (95% confidence interval [CI], 0.12-0.23; P <.0001). The 2-year DFS rate was 90% with osimertinib compared with 44% with placebo. In the overall population, the DFS HR was 0.21 (95% CI, 0.16-0.28; P <.0001). The 2-year DFS rate was 89% with osimertinib compared with 53% with placebo. OS data were immature at the time of data cutoff. The safety profile of osimertinib was consistent with prior reports.
Researchers concluded that adjuvant osimertinib is the first targeted agent evaluated in a global trial that shows a statistically significant and clinically meaningful improvement in DFS in patients with stage IB, stage II, and stage IIIA EGFR-mutated NSCLC after complete tumor resection and adjuvant chemotherapy (when indicated). Adjuvant osimertinib provides an effective new treatment strategy for these early-stage patients.
- Herbst RS, Tsuboi M, John T, et al. Osimertinib as adjuvant therapy in patients with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. J Clin Oncol. 2020;38:suppl (abstract LBA5).