Adjuvant Osimertinib Shows Long-Term DFS Benefit in Resected EGFR-Mutated NSCLC


Results from the final disease-free survival analysis of the phase 3 ADAURA trial confirm the benefit of osimertinib vs placebo for the treatment of EGFR-positive non–small cell lung cancer.

Roy S. Herbst, MD, PhD

Roy S. Herbst, MD, PhD

The use of adjuvant osimertinib (Tagrisso) has demonstrated prolonged disease-free survival (DFS) in comparison with placebo, reduced the risk of local and distant metastases, and improved central nervous system (CNS) DFS in patients with EGFR-mutated stage IB-IIIA non–small cell lung cancer (NSCLC), in the ADAURA trial (NCT02511106).1

In the phase 3, double-blind, randomized, placebo-controlled, multicenter study, adjuvant osimertinib also demonstrated a safety profile that was consistent with that observed in prior studies. According to the study investigators led by Roy S. Herbst, MD, PhD these findings support the use of adjuvant osimertinib in patients with resected EGFR-mutated NSCLC.

“These data demonstrate a new paradigm demonstrating the importance of using targeted therapy against epidermal growth-factor-driven tumors as early as possible in the course of a patient’s disease,” said Herbst, lead author and principal investigator of the ADUARA trial, Ensign Professor of Medicine (Medical Oncology), and professor of pharmacology and deputy director at Yale Cancer Center. “The results have led to a new standard of care in this disease setting.”

At total of 682 patients with stage IB-IIIA EGFR-mutated NSCLC were included in the study and randomized 1:1 to receive either osimertinib 80 mg once daily or placebo for a 3-year period. The patients were evaluated for the primary end point of DFS by investigator assessment and the secondary end points which included DFS in stage IB-IIIA, overall survival (OS), and safety. As an exploratory end point, investigators also assessed patterns of disease recurrence and CNS DFS.

Overall, 339 patients were treated with osimertinib in the study, and 343 received placebo. The study arms were well balanced with the majority of patients being females aged < 65 years. The population was predominantly Asian with an exon 19 deletion, and most had received chemotherapy in the adjuvant setting.

The median DFS among patients treated with osimertinib was 65.8 months (95% CI, 61.7 months-not calculated [NC]) vs 28.1 months (95% CI, 22.1-35.0 months) in the placebo arm. Seventy-three percent (95% CI, 67-78) of patients were still alive and disease-free at 48 months in the osimertinib arm compared with 38% (95% CI, 32-43) in the placebo arm. The DFS benefit was carried across to all predefined subgroups. In terms of the secondary end point of DFS by stage of disease, a benefit was shown across all stages after restaging.

Disease recurrence occurred in 27% of the osimertinib arm compared with 60% of the placebo arm. In the majority of the osimertinib-treated patients, recurrences were distant only, but in the placebo-treated population, most with local. Recurrence appeared in various locations among patients in both treatment arms. Most patients in either arm had recurrence in the lung or CNS.

Among the patients with a CNS recurrence, the CNS DFS was not reached in the osimertinib group (95% CI, 65.8-NC) vs NR in the placebo group (95% CI, NC-NC), for a difference of (HR, 0.24; 95% CI, 0.14-0.42).

All patients were evaluated for safety, and adverse events occurred in 98% of the osimertinib population vs 90% of the placebo group. The most common any-grade AEs in all patients were diarrhea (47%), paronychia (27%), dry skin (25%), pruritus (21%), and cough (20%). In addition, cardiac effects were reported in 6% of the osimertinib arm vs 3% of the placebo arm.

Adjuvant osimertinib is already an FDA-approved option for patients with resected EGFR-mutated NSCLC, based on earlier results from ADAURA.2 Mature DFS data from the updated analysis underscore the importance of conducting routine EGFR testing at the time of diagnosis, according to Herbst et al. Data points to be reported from ADUARA in the future include long-term safety, subsequent treatment patterns, and updated OS.1


1. Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: updated results from the phase iii randomized ADAURA trial. J Clin Oncol. Published online January 31, 2023. doi: 10.1200/JCO.22.02186

2. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. News release. FDA. December 18, 2020. Accessed February 2, 2023.

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