Clinical trialPhase 3Lung cancer

Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC

N Engl J Med · 2023682 patients

Tsuboi M, Herbst RS, John T, Kato T, Majem M, Grohé C, et al. N Engl J Med. 2023. 389:137-147

Study type: Clinical trial
Study name: ADAURA
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial (1:1)
Sample size: 682 patients
Source: N Engl J Med · 2023
Trial registration: NCT02511106

In plain words

If your lung cancer has been completely removed by surgery and the tumour has an EGFR mutation, taking an osimertinib tablet every day for up to 3 years after surgery (and after chemotherapy, if needed) clearly increases the chance of staying alive: in this study, after 5 years 88% of patients in the osimertinib group were alive compared with 78% in the placebo group. This is why testing the surgical sample for EGFR is so important.

Key results

85% vs 73%

5-year overall survival (stage II–IIIA)

HR for death 0.49; 95.03% CI 0.33–0.73; P<0.001

88% vs 78%

5-year overall survival (overall population IB–IIIA)

HR 0.49; 95.03% CI 0.34–0.70; P<0.001

Median not reached vs 19.6 months

Disease-free survival (stage II–IIIA, primary analysis)

HR 0.17; 95% CI 0.12–0.23; P<0.0001 (FDA label)

Median not reached vs 27.5 months

Disease-free survival (overall population IB–IIIA)

HR 0.20; 95% CI 0.15–0.27; P<0.0001 (FDA label)

Drugs in this study:Osimertinib (Tagrisso)

Dose and schedule cards

Adjuvant osimertinib (ADAURA)

Resected stage IB–IIIA NSCLC with an EGFR exon 19 deletion or L858R mutationCycle length: ContinuousOn the page “Lung cancer” · Resectable NSCLC: treatment before or after surgery

Resected stage IB–IIIA NSCLC with an EGFR exon 19 deletion or L858R mutation

Drug	Dose	Route	Schedule
Osimertinib	80 mg	Oral, with or without food	Once daily, continuous

Cycle length: Continuous
Duration: 3 years in total, or until recurrence or intolerable toxicity

Source: FDA label for osimertinib; trial. Before starting: CBC and, in patients with cardiac risk factors, LVEF. QTc greater than 500 ms on two ECGs: withhold until below 481, then resume at 40 mg. Interstitial lung disease of any grade (without recent chemoradiotherapy): discontinue permanently. If a strong CYP3A4 inducer cannot be avoided, increase the dose to 160 mg daily.

On the page “Lung cancer” · Resectable NSCLC: treatment before or after surgery

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Osimertinib

Osimertinib 80 mg orally once daily (with or without food); dose reduction to 40 mg once daily was allowed. Treatment duration: 3 years or until disease recurrence or unacceptable toxicity. Started after recovery from surgery and standard adjuvant chemotherapy (if given): randomisation up to 10 weeks after surgery in patients without adjuvant chemotherapy and up to 26 weeks in patients who had received adjuvant chemotherapy.

2Placebo

Matching oral placebo once daily under the same rules (maximum 3 years). After recurrence, open-label osimertinib was offered to eligible patients.

Source of the regimen details: FDA label for Tagrisso (DailyMed, sections 14.1 and 2.3, September 2026 version), ClinicalTrials.gov NCT02511106 (dose reduction to 40 mg) and the abstract of the paper

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with completely resected NSCLC of predominantly non-squamous histology, stage IB to IIIA (AJCC 7th edition), with an EGFR exon 19 deletion or exon 21 L858R mutation prospectively confirmed on tumour tissue in a central laboratory (cobas test); with or without prior adjuvant chemotherapy. Exclusion criteria: uncontrolled clinically significant cardiac disease, a history of ILD/pneumonitis and prior treatment with any EGFR inhibitor. Randomisation was stratified by mutation type, race (Asian or non-Asian) and stage.

Endpoints

Primary endpoint: investigator-assessed disease-free survival (DFS) in stage II to IIIA. Secondary: DFS in the overall population (IB to IIIA), overall survival and safety. This paper is the planned final analysis of overall survival.

Safety and side effects

According to the FDA label (DFS analysis; median exposure 22.5 months, 337 patients): serious adverse events in 16% (most common pneumonia 1.5%); dose reduction due to an adverse event 9% and permanent discontinuation 11% (mainly interstitial lung disease 2.7% and rash 1.2%). The most common adverse events (all grades, versus placebo): diarrhoea 47% (grade 3: 2.4%), rash 40%, nail toxicity 37%, stomatitis 32% (grade 3: 1.8%), dry skin 29%. Interstitial lung disease (ILD) 3%; LVEF decrease of ≥10 percentage points to below 50% in 1.5%. In the final overall survival analysis, the safety profile was consistent with the primary analysis and only one new serious adverse event (COVID-19 pneumonia, unrelated to the drug) was reported.

Clinical significance and place in guidelines

ADAURA made adjuvant osimertinib the standard of care for resected stage IB to IIIA EGFR-mutated NSCLC (FDA approval in 2020 based on DFS). Demonstrating an overall survival benefit answered the criticism that it merely "delays recurrence". The ESMO and NCCN guidelines recommend EGFR testing in resected patients and adjuvant osimertinib in these patients.

Limitations

The control group received placebo, and control patients did not always have access to osimertinib at recurrence; staging was based on the AJCC 7th edition, without mandatory PET or brain MRI in all patients; the optimal treatment duration (3 years versus longer) is still unknown.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.