Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer
- Study type
- Clinical trial
- Study name
- AURA3
- Phase
- Phase 3
- Design
- Randomised, international, open-label trial
- Sample size
- 419 patients
- Source
- N Engl J Med · 2017
- Trial registration
- NCT02151981
In plain words
In this study, patients with advanced lung cancer with the T790M mutation, whose first targeted medicine (an EGFR inhibitor) had stopped working, received either osimertinib tablets or chemotherapy. Patients taking osimertinib stayed free of disease progression for longer (10.1 months versus 4.4 months). Serious side effects were less common in the osimertinib group, and this medicine also worked better in patients whose cancer had spread to the brain or central nervous system.
Key results
Treatment arms and regimens
Osimertinib 80 mg orally once daily (2:1 allocation; 279 patients), until disease progression, unacceptable toxicity or patient or physician request; continuation of treatment after progression (RECIST 1.1) was allowed if there was clinical benefit in the investigator's opinion.
Pemetrexed 500 mg/m² IV plus carboplatin AUC 5 or cisplatin 75 mg/m² IV, on day 1 of 21-day cycles (every 3 weeks) for up to 6 cycles (140 patients). Patients without progression after 4 cycles could continue maintenance pemetrexed per the drug label. After confirmed disease progression (investigator assessment and central imaging confirmation), crossover to osimertinib 80 mg daily was possible.
In practice: 74% received at least 4 cycles of platinum-pemetrexed and 54% received maintenance pemetrexed; 60% of patients in this group later crossed over to osimertinib.
Source of the regimen details: Full text of the paper (PMC6762027) and ClinicalTrials.gov NCT02151981
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 histologically or cytologically documented locally advanced or metastatic NSCLC whose disease had progressed during first-line EGFR-TKI therapy; a documented EGFR mutation and central confirmation of the T790M mutation (cobas EGFR test) after first-line therapy were required; a blood sample was also taken to test for T790M in plasma ctDNA. Stable, asymptomatic central nervous system metastases not requiring glucocorticoids for at least 4 weeks before starting the drug were allowed.
Endpoints
Primary endpoint: investigator-assessed progression-free survival (PFS).
Safety and side effects
Grade 3 or higher adverse events were less frequent with osimertinib (23% versus 47% with platinum plus pemetrexed). Interstitial lung disease (ILD)-like events occurred in 4% of the osimertinib group (9 grade 1 or 2 events and one death) and 1% of the chemotherapy group; QT prolongation in 4% versus 1% (all grade 1 or 2 except one grade 3 event). Permanent discontinuation due to adverse events: 7% versus 10%. Fatal adverse events: 4 patients in the osimertinib group (respiratory failure 2, pneumonitis 1, ischaemic stroke 1) and one patient in the chemotherapy group (hypovolaemic shock).
Clinical significance and place in guidelines
This trial shows that in patients with advanced T790M-positive non-small-cell lung cancer after disease progression on first-line EGFR-TKI therapy, osimertinib is superior in efficacy to platinum plus pemetrexed chemotherapy. The status of drug approvals and clinical guideline recommendations should be checked separately, as they are not mentioned in the abstract.
Limitations
The trial was open-label and the primary endpoint was assessed by the investigator. Other limitations are not given in the abstract.
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.