Perioperative Durvalumab for Resectable Non–Small-Cell Lung Cancer
- Study type
- Clinical trial
- Study name
- AEGEAN
- Phase
- Phase 3
- Design
- Phase 3 randomised, double-blind, multicentre, placebo-controlled trial (1:1), stratified by disease stage and PD-L1 expression
- Sample size
- 802 patients (400 in the durvalumab group and 402 in the placebo group)
- Source
- N Engl J Med · 2023
- Trial registration
- NCT03800134
In plain words
In this study, patients with non-small-cell lung cancer who could have surgery were given chemotherapy before the operation together with either the immunotherapy drug durvalumab or a placebo, and the same drug (durvalumab or placebo) was continued after surgery. Patients who had durvalumab stayed longer without their disease getting worse, coming back or death, and their surgical samples more often showed that no living cancer cells were left. The rate of serious side effects was about the same in the two groups.
Key results
Treatment arms and regimens
Neoadjuvant: durvalumab 1500 mg IV on day 1 (before chemotherapy on the same day) every 3 weeks for 4 cycles, with histology-based platinum chemotherapy (4 cycles):
- Squamous histology: carboplatin AUC 6 + paclitaxel 200 mg/m² on day 1; or cisplatin 75 mg/m² on day 1 + gemcitabine 1250 mg/m² on days 1 and 8
- Non-squamous: pemetrexed 500 mg/m² + cisplatin 75 mg/m² on day 1; or pemetrexed 500 mg/m² + carboplatin AUC 5 on day 1
In case of intolerance, switching from cisplatin to carboplatin was allowed at any time, and in patients with comorbidities or unable to tolerate cisplatin, carboplatin AUC 5 was allowed from cycle 1. All drugs IV. Surgery within 40 days after the last neoadjuvant dose.
Adjuvant: durvalumab 1500 mg IV every 4 weeks for up to 12 cycles after surgery, or until recurrence or unacceptable toxicity. (FDA label for weight <30 kg: 20 mg/kg.)
Neoadjuvant: IV placebo on day 1 every 3 weeks for 4 cycles, with the same platinum chemotherapy:
- Squamous histology: carboplatin AUC 6 + paclitaxel 200 mg/m² on day 1; or cisplatin 75 mg/m² on day 1 + gemcitabine 1250 mg/m² on days 1 and 8
- Non-squamous: pemetrexed 500 mg/m² + cisplatin 75 mg/m² on day 1; or pemetrexed 500 mg/m² + carboplatin AUC 5 on day 1
In case of intolerance, switching from cisplatin to carboplatin was allowed at any time, and in patients with comorbidities or unable to tolerate cisplatin, carboplatin AUC 5 was allowed from cycle 1. All drugs IV. Surgery within 40 days after the last neoadjuvant dose.
Adjuvant: IV placebo every 4 weeks for up to 12 cycles after surgery.
Source of the regimen details: FDA label for Imfinzi (DailyMed, sections 14.1 and 2.2, September 2026 version) and ClinicalTrials.gov NCT03800134 (timing of surgery)
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
Patients with previously untreated resectable NSCLC, squamous or non-squamous, stage IIA to selected IIIB (N2) according to the AJCC 8th edition, with WHO/ECOG performance status 0 or 1, at least one target lesion according to RECIST 1.1 and no prior exposure to immunotherapy; regardless of PD-L1 expression. Exclusion criteria: active or prior autoimmune disease and use of immunosuppressive drugs within 14 days before the first dose. Randomisation was stratified by stage (II or III) and PD-L1 (≥1% or <1%). Data from 62 patients with documented EGFR or ALK alterations were excluded from the efficacy analyses (modified intention-to-treat population).
Endpoints
Primary endpoints: event-free survival (time to the first occurrence of disease progression that precluded surgery or prevented completion of surgery, disease recurrence [assessed by blinded independent central review] or death from any cause) and pathological complete response (assessed centrally).
Safety and side effects
Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients in the durvalumab group and 43.2% in the placebo group; the safety profile was consistent with the individual agents. According to the FDA label, neoadjuvant phase: serious adverse events 21% (pneumonia 2.7%), fatal adverse events 2%, permanent discontinuation of any drug 14% and of durvalumab 6.7%; surgery cancelled because of an adverse event 1.7% versus 1%, and surgery delayed 4% in each group. Adjuvant phase: serious adverse events 13% (pneumonia 1.9%, pneumonitis 1.1%), permanent discontinuation of durvalumab 8%.
Clinical significance and place in guidelines
According to the abstract, adding durvalumab to neoadjuvant chemotherapy and continuing it after surgery improved event-free survival and pathological complete response in resectable stage II to IIIB (N2) NSCLC, without an apparent increase in grade 3 or 4 adverse events. Patients with EGFR or ALK alterations were excluded from the efficacy analyses. The status of drug approvals and clinical guideline recommendations for this regimen should be checked in up-to-date sources.
Limitations
According to the abstract, the event-free survival results come from the first interim analysis, and data from 62 patients with EGFR or ALK alterations were excluded from the efficacy analyses. The P<0.001 result for pathological complete response relates to the interim analysis of data from 402 patients. Overall survival and long-term follow-up data are not reported in the abstract. The study was funded by AstraZeneca.
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.