ADAURA Results: Osimertinib as Adjuvant Therapy for EGFR-Mutated NSCLC

Adjuvant osimertinib use results in clinically meaningful improvement in disease-free survival for patients with NSCLC who undergo surgery for early-stage disease.

Osimertinib (Tagrisso), a third-generation central nervous system–active EGFR-targeting tyrosine kinase inhibitor, is approved for use in patients with advanced NSCLC. ADAURA is a phase 3, double-blind, randomized study that assessed 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.¹ Following independent data monitoring committee recommendations, the trial was unblinded early due to efficacy.¹ This report summarizes an unplanned interim data analysis.¹

Eligible patients had to be aged ≥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.¹ Postoperative chemotherapy was allowed. The maximum interval between surgery and study randomization was 10 weeks without adjuvant chemotherapy and 26 weeks with adjuvant chemotherapy.¹

Patients were randomized to either osimertinib (80 mg orally once daily) or placebo and received treatment for up to 3 years.¹ Patients were stratified by disease stage (IB, II, IIIA), mutation type (ex19del vs L858R), and race (Asian vs non-Asian).¹ The primary end point of the study was disease-free survival (DFS) by investigator in stage II to IIIA patients. Secondary end points included OS and safety.¹

In total, 682 patients were randomized to treatment: 339 to osimertinib and 343 to placebo.¹ Baseline characteristics were balanced between the osimertinib and placebo arms: stage IB, 31% versus 31%, respectively; stage II or IIIA, 69% versus 69%, respectively; female, 68% versus 72%, respectively; ex19del, 55% versus 56%, respectively; and L858R, 45% versus 44%, respectively.¹ Just over half (55%) of patients received adjuvant chemotherapy before study randomization.¹

Among stage II and stage IIIA patients, the DFS HR was 0.17 in favor of osimertinib compared with placebo (95% CI, 0.12-0.23; P <.0001).¹ The 2-year DFS rate was 90% with osimertinib compared with 44% with placebo.¹ In the overall population, the DFS HR was 0.21 (95% CI, 0.16-0.28; P <.0001).¹ The 2-year DFS rate was 89% with osimertinib compared with 53% with placebo.¹ OS data were immature at the time of data cutoff.¹ The safety profile of osimertinib was consistent with previous reports.¹

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.¹

Reference
1. Herbst RS, Tsuboi M, John T, et al. Osimertinib as adjuvant therapy in patients (pts) with stage IB-IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. J Clin Oncol. 2020;38(18_suppl). Abstract LBA5.