Osimertinib ( Tagrisso ) is a 3rd-generation, CNS-active, epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor ( TKI ) [ EGFR-TKI ] with superior efficacy to comparator EGFR-TKI ( Gefitinib / Erlotinib ) in treatment-naïve EGFR mutation positive ( EGFRm ) advanced non-small-cell lung cancer ( NSCLC ).
Approximately 30% of patients with NSCLC present with early stage ( I–IIIA ) disease; surgery is the primary treatment.
Adjuvant chemotherapy is standard of care in patients with resected stage II–III NSCLC and select stage IB patients; however, recurrence rates are high and other therapies are needed.
ADAURA is a phase III, double-blind, randomized study assessing the efficacy and safety of Osimertinib versus placebo in patients with stage IB–IIIA EGFRm NSCLC after complete tumor resection and adjuvant chemotherapy, when indicated.
Following IDMC ( Independent Data Monitoring Committee ) recommendation, the trial was unblinded early due to efficacy.
Researchers have reported an unplanned interim analysis.
Eligible patients were: 18 years or more ( Japan / Taiwan: 20 or more ), WHO PS 0/1, primary non-squamous stage IB/II/IIIA NSCLC, confirmed EGFRm ( ex19del/L858R ), complete resection of primary NSCLC with full recovery from surgery; postoperative chemotherapy was allowed.
Patients were randomized 1:1 to Osimertinib 80 mg once daily orally or placebo to receive treatment for up to 3 years and stratified by stage ( IB/II/IIIA ), mutation type ( ex19del/L858R ), and race ( Asian / non-Asian ).
Primary endpoint was disease-free survival ( DFS ) by investigator in stage II–IIIA patients. Secondary endpoints was overall survival ( OS ) and safety.
Data cutoff was 17 Jan 2020.
Globally, 682 patients were randomized to treatment: Osimertinib n=339, placebo n=343.
Baseline characteristics were balanced across arms ( Osimertinib / placebo ): stage IB 31/31%, stage II/IIIA 69/69%, female 68/72%, ex19del 55/56%, L858R 45/44%.
In stage II–IIIA patients, DFS hazard ratio ( HR ) was 0.17 ( 95% CI 0.12, 0.23 ); p less than 0.0001 ( 156/470 events ); 2-year DFS rate was 90% with Osimertinib versus 44% with placebo.
In the overall population, DFS hazard ratio was 0.21 ( 0.16, 0.28 ); p less than 0.0001 ( 196/682 events ); 2-year DFS rate was 89% with Osimertinib vs 53% with placebo.
Overall survival ( OS ) was immature ( 4% maturity ) with 29/682 deaths ( Osimertinib n=9, placebo n=20 ) at data cutoff.
The safety profile was consistent with the known safety profile of Osimertinib.
In conclusion, adjuvant Osimertinib is the 1st targeted agent in a global trial to show a statistically significant and clinically meaningful improvement in disease-free survival in patients with stage IB/II/IIIA EGFRm NSCLC after complete tumor resection and adjuvant chemotherapy, when indicated.
Adjuvant Osimertinib provides an effective new treatment strategy for these patients. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020