Clinical trialPhase 3Lung cancer

Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC

N Engl J Med · 2024216 patients

Lu S, Kato T, Dong X, Ahn MJ, Quang LV, Soparattanapaisarn N, et al. N Engl J Med. 2024. 391:585-597

Study type: Clinical trial
Study name: LAURA
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial (approximately 2:1 allocation)
Sample size: 216 patients
Source: N Engl J Med · 2024
Trial registration: NCT03521154

In plain words

In stage III lung cancer that cannot be operated on, the main treatment is chemotherapy and radiotherapy given together. If the tumour has an EGFR mutation, taking an osimertinib tablet every day after chemoradiotherapy ended extended the time the disease stayed under control from about 6 months to more than 3 years. Data on survival are not yet complete.

Key results

39.1 vs 5.6 months

Median progression-free survival

HR 0.16; 95% CI 0.10–0.24; P<0.001

74% vs 22%

Alive and progression-free at 12 months

84% vs 74%

36-month overall survival (interim analysis, 20% maturity)

HR 0.81; 95% CI 0.42–1.56; P=0.53

Drugs in this study:Osimertinib (Tagrisso)Durvalumab (Imfinzi)

Dose and schedule cards

Osimertinib after chemoradiotherapy (LAURA)

Unresectable stage III NSCLC with an EGFR exon 19 deletion or L858R, without progression after concurrent or sequential platinum-based chemoradiotherapyCycle length: ContinuousOn the page “Lung cancer” · Unresectable stage III NSCLC: chemoradiotherapy and consolidation therapy

Unresectable stage III NSCLC with an EGFR exon 19 deletion or L858R, without progression after concurrent or sequential platinum-based chemoradiotherapy

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

Cycle length: Continuous
Duration: Until disease progression or intolerable toxicity

Source: FDA label for osimertinib; trial. In LAURA, pneumonitis (including radiation pneumonitis) occurred in 56% of the osimertinib group vs 38% of the placebo group (grade 3: 3.5%). After recent chemoradiotherapy: grade 1 pneumonitis → continue or withhold according to the clinical situation; grade 2 or higher → discontinue permanently.

On the page “Lung cancer” · Unresectable stage III NSCLC: chemoradiotherapy and consolidation therapy

Consolidation durvalumab after chemoradiotherapy (PACIFIC)

Unresectable stage III NSCLC without progression after at least 2 cycles of platinum chemotherapy concurrent with radiotherapy; WHO PS 0–1; with an EGFR mutation, osimertinib (next regimen) is preferredCycle length: Every 14 or 28 daysOn the page “Lung cancer” · Unresectable stage III NSCLC: chemoradiotherapy and consolidation therapy

Drug	Dose	Route	Schedule
Durvalumab	10 mg/kg every 2 weeks or 1500 mg every 4 weeks (body weight ≥30 kg)	IV (60 min)	Start within 42 days after the end of chemoradiotherapy

Cycle length: Every 14 or 28 days
Duration: Up to 12 months, or until progression or intolerable toxicity

Source: FDA label for durvalumab; 5-year results. In PACIFIC, pneumonitis (including radiation pneumonitis) occurred in 18.3% of the durvalumab group vs 12.8% of the placebo group.

On the page “Lung cancer” · Unresectable stage III NSCLC: chemoradiotherapy and consolidation therapy

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. Continued until disease progression (by blinded independent central review), unacceptable toxicity or other discontinuation criteria; no fixed time limit. Randomisation up to 6 weeks after the end of chemoradiotherapy (143 patients). After progression, open-label osimertinib was offered to patients in both groups.

2Placebo

Matching oral placebo once daily until disease progression or unacceptable toxicity (73 patients); after progression, open-label osimertinib could be given.

Source of the regimen details: FDA label for Tagrisso (DailyMed, sections 14 and 2.3, September 2026 version) and ClinicalTrials.gov NCT03521154 (dose reduction to 40 mg)

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 unresectable locally advanced stage III NSCLC with an EGFR exon 19 deletion or L858R mutation (cobas v2 test in a central laboratory or an FDA-approved test), without progression during or after definitive platinum-based chemoradiotherapy (concurrent or sequential; at least 2 three-weekly cycles or 5 weekly doses of platinum with definitive radiotherapy, completed no more than 6 weeks before randomisation); WHO performance status 0 or 1. Exclusion criteria: grade ≥2 pneumonitis after chemoradiotherapy or any prior ILD. 2:1 allocation stratified by type of chemoradiotherapy (concurrent/sequential), stage (IIIA versus IIIB/IIIC) and region (China/other).

Endpoints

Primary endpoint: progression-free survival (PFS) assessed by blinded independent central review. Secondary: overall survival and safety.

Safety and side effects

Grade 3 or higher adverse events: 35% with osimertinib versus 12% with placebo. Radiation pneumonitis (mostly grade 1 to 2) was reported in 48% versus 38%. According to the FDA label: ILD/pneumonitis (including radiation pneumonitis) in 56% of osimertinib patients versus 38% with placebo (grade 3: 3.5%; one fatal case, 0.7%); ILD/pneumonitis led to permanent discontinuation in 7% and dose interruption in 35%. Serious adverse events 38%; permanent discontinuation due to adverse events 13%, dose interruption 56% and dose reduction 8%. No new safety concerns emerged.

Clinical significance and place in guidelines

LAURA made consolidation osimertinib the new standard for unresectable stage III EGFR-mutated NSCLC (FDA approval in September 2024), replacing durvalumab (the PACIFIC regimen) in this subgroup, in which the benefit of immunotherapy is uncertain. The finding underlines the need to determine EGFR status before starting consolidation therapy.

Limitations

Overall survival data are immature and crossover of placebo patients to osimertinib after progression was allowed; treatment has no time limit and its optimal duration is unknown; radiation pneumonitis was more frequent in the osimertinib group.

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.