Adjuvant Osimertinib Sustains 8-Year OS Benefit in Resected EGFR+ NSCLC

An exploratory long-term analysis of the phase 3 ADAURA trial (NCT02511106) found that adjuvant osimertinib (Tagrisso) continued to extend overall survival (OS) relative to placebo 8 years after treatment began in patients with resected, EGFR-mutated non–small cell lung cancer (NSCLC), according to data presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) and published in the Journal of Thoracic Oncology.^1,2

Among patients with stage II-IIIA disease, the trial’s primary population, osimertinib was associated with a 47% lower risk of death than placebo (HR, 0.53; 95% CI, 0.38-0.75; 142 of 470 events); 74% of osimertinib-treated patients were alive at 8 years (95% CI, 67%-80%) compared with 58% of those who received placebo (95% CI, 50%-65%).

Across the full stage IB-IIIA cohort, the risk of death was 48% lower with osimertinib (HR, 0.52; 95% CI, 0.39-0.71; 175 of 682 events), with 8-year OS rates of 79% (95% CI, 74%-83%) versus 64% (95% CI, 58%-70%) for placebo. The survival advantage held across every prespecified subgroup analyzed.

“These ADAURA findings show patients continue to experience meaningful, long-term benefit following early intervention with adjuvant osimertinib, with a [16%] improvement in [OS at 8 years vs] placebo,” Roy S. Herbst, MD, PhD, director at Dartmouth Cancer Center and principal investigator of the ADAURA trial, stated in a news release.³ “This is especially impressive given high rates of crossover to osimertinib following disease recurrence. This durable [OS] benefit reinforces the importance of [prioritizing] EGFR testing at diagnosis so as many patients as possible can benefit from this transformative therapy.”

Background and Trial Design

ADAURA randomly assigned 682 patients with completely resected, stage IB, II, or IIIA EGFR-mutated NSCLC to receive either osimertinib at 80 mg daily (n = 339) or placebo (n = 343) for up to 3 years, with treatment stopping earlier for recurrence or another qualifying reason.^1,2

Eligible patients were 18 years or older (20 years or older in Taiwan and Japan) with a performance status of 0 or 1, and adjuvant chemotherapy was allowed at the discretion of treating physicians and patients. Enrollment spanned more than 200 sites across over 20 countries in North America, Europe, South America, Asia, and the Middle East. Investigator-assessed disease-free survival (DFS) in the stage II-IIIA subgroup was the trial’s primary end point, whereas DFS in the broader stage IB-IIIA population and OS in both populations served as key secondary end points.

At the original DFS/OS readout, osimertinib had already shown a significant advantage over placebo for both DFS (HR, 0.20; P <.001) and OS (HR, 0.49; P <.001), with median OS follow-up at that time of 60.4 months in the osimertinib group and 59.4 months in the placebo group.

Designing the Exploratory Analysis

Investigators built this post hoc OS analysis from data on all randomized patients. For the subset still alive when the trial’s planned final OS analysis occurred (data cutoff, January 27, 2023; n = 558), the team gathered additional annual follow-up information with renewed patient consent through a new cutoff of May 4, 2026, supplementing this with medical-record or last-contact data for 431 patients. The remaining 127 patients without newer survival information were treated as censored at their last confirmed alive date from the original analysis.

By the time of this update, every enrolled patient had already had the opportunity to finish the full 3-year adjuvant course. Median OS follow-up reached 92.0 months for those who received osimertinib and 68.5 months for those receiving placebo in the primary population, and 93.3 months vs 79.6 months in the overall population.

Safety data, collected through the earlier planned final analysis, showed no new concerns and remained in line with osimertinib’s known tolerability profile.

Real-World Findings Show Importance of Treatment Duration

A separate retrospective cohort study of 822 US patients with stage I-IIIA EGFR-mutant NSCLC was also presented at the conference, showing that patients who stopped osimertinib before completing the full 3-year regimen faced a 2.3-fold increase in risk of recurrence or death in an adjusted 12-month landmark analysis and 2.7-fold increase in risk in a 24-month analysis vs those who completed treatment, underscoring the value of completing the treatment course of EGFR inhibition.⁴

Among 336 patients who discontinued therapy, 39 (12%) had disease recurrence within a 30-day range, 154 (46%) had an adverse event in that range without recurrence, and 143 (43%) had neither, leading the investigators to advise proactive risk management as well as counseling patients on the importance of completing therapy.

“ADAURA continues to set new benchmarks in early-stage EGFR-mutated lung cancer, with nearly 80 percent of patients treated with adjuvant [osimertinib] alive at [8] years,” said Susan Galbraith, MD, PhD, executive vice president of oncology hematology research and development at AstraZeneca, in the news release.³ “These results underscore the importance of treating early and reinforce [osimertinib] as the adjuvant standard of care and backbone therapy across stages of the disease.”

The investigators described this update as the longest OS follow-up yet reported from a global phase 3 adjuvant trial in EGFR-mutated NSCLC, offering further confirmation of durable benefit from adjuvant osimertinib administered with or without chemotherapy in patients with resected stage IB-IIIA disease.¹

REFERENCES

1. Herbst RS, Majem M, John T, et al. Adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA NSCLC: ADAURA exploratory 8-year overall survival landmark update. Presented at: IASLC 2026 World Conference on Lung Cancer; September 14, 2026; Seoul, Republic of Korea. Abstract PL03.01.

2. Wu Y-L, Majem M, John T, et al. Adjuvant osimertinib in resected EGFR-Mutated stage IB–IIIA non-small cell lung cancer: exploratory 8-year overall survival landmark update from the ADAURA trial [161/175]. J Thorac Oncol. Published online September 14, 2026. doi:10.1016/j.jtho.2026.104179

3. Tagrisso demonstrated unprecedented eight-year landmark survival in early-stage EGFR-mutated lung cancer in ADAURA Phase III trial. News release. AstraZeneca. Presented at: IASLC 2026 World Conference on Lung Cancer; September 14, 2026; Seoul, Republic of Korea. Accessed September 14, 2026. https://tinyurl.com/bdexy2hz

4. Singhi E, Ma X, Rinaldi C, et al. Real-world treatment duration and outcomes among patients with early-stage nsclc receiving adjuvant osimertinib: a retrospective cohort study. Presented at: IASLC 2026 World Conference on Lung Cancer; September 14, 2026; Seoul, Republic of Korea. Abstract P1.142.