Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial

Abstract

Purpose: The phase III ADAURA (ClinicalTrials.gov identifier: NCT02511106) primary analysis demonstrated a clinically significant disease-free survival (DFS) benefit with adjuvant osimertinib versus placebo in EGFR-mutated stage IB-IIIA non-small-cell lung cancer (NSCLC) after complete tumor resection (DFS hazard ratio [HR], 0.20 [99.12% CI, 0.14 to 0.30]; P < .001). We report an updated exploratory analysis of final DFS data.

Methods: Overall, 682 patients with stage IB-IIIA (American Joint Committee on Cancer/Union for International Cancer Control, seventh edition) EGFR-mutated (exon 19 deletion/L858R) NSCLC were randomly assigned 1:1 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years. The primary end point was DFS by investigator assessment in stage II-IIIA disease analyzed by stratified log-rank test; following early reporting of statistical significance in DFS, no further formal statistical testing was planned. Secondary end points included DFS in stage IB-IIIA, overall survival, and safety. Patterns of recurrence and CNS DFS were prespecified exploratory end points.

Results: At data cutoff (April 11, 2022), in stage II-IIIA disease, median follow-up was 44.2 months (osimertinib) and 19.6 months (placebo); the DFS HR was 0.23 (95% CI, 0.18 to 0.30); 4-year DFS rate was 70% (osimertinib) and 29% (placebo). In the overall population, DFS HR was 0.27 (95% CI, 0.21 to 0.34); 4-year DFS rate was 73% (osimertinib) and 38% (placebo). Fewer patients treated with osimertinib had local/regional and distant recurrence versus placebo. CNS DFS HR in stage II-IIIA was 0.24 (95% CI, 0.14 to 0.42). The long-term safety profile of osimertinib was consistent with the primary analysis.

Conclusion: These updated data demonstrate prolonged DFS benefit over placebo, reduced risk of local and distant recurrence, improved CNS DFS, and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.

FIG 1.

DFS per investigator assessment. Kaplan-Meier estimates of duration of (A) DFS in patients with stage II-IIIA disease and (B) in the overall population (stage IB-IIIA) by seventh edition staging per the protocol (full analysis set). Tick marks indicate censored data. An HR < 1 favors osimertinib. DFS, disease-free survival; HR, hazard ratio; NC, not calculated.

FIG 2.

Disease-free survival subgroup analysis per investigator assessment (full analysis set; overall population). The subgroup analysis was performed using a Cox proportional hazards model including treatment, subgroup, and a treatment-by-subgroup interaction term. An HR < 1 favors osimertinib. EGFR, epidermal growth factor receptor; HR, hazard ratio.

FIG 3.

CNS analyses (full analysis set; stage II-IIIA). Kaplan-Meier estimates of duration of (A) CNS DFS per investigator assessment in patients with stage II-IIIA disease. Tick marks indicate censored data. An HR < 1 favors osimertinib. (B) Conditional probability of observing CNS and non-CNS recurrence. The graph shows the estimated probability of observing CNS recurrence event, conditional on the patient not experiencing a competing risk event (non-CNS recurrence and death by any cause) by time t. Cumulative incidence was calculated using a Fine and Gray model. CNS disease recurrence includes patients who have disease recurrence in the CNS alone or in the CNS in addition to other anatomies at the same overall visit. Non-CNS recurrence includes disease recurrence outside the CNS only. Death was defined as death occurring without confirmed CNS or non-CNS recurrence. DFS, disease-free survival; HR, hazard ratio; NC, not calculated; NR, not reached.