Lung cancer is a leading cause of cancer-related death. In East Asian non-small cell lung cancer (NSCLC) patients, epidermal growth factor receptor (EGFR) mutations occur in 40-55% of lung adenocarcinomas.¹Guo Y et al. Front Oncol. 2020;10. Treatment for EGFR-mutation positive NSCLC in the first-line setting are EGFR tyrosine kinase inhibitors (TKIs).¹Guo Y et al. Front Oncol. 2020;10. Based on the ADAURA trial results, Osimertinib – a third-generation EGFR-TKI –  the United States Food and Drug Administration (USFDA) is now approved as the first adjuvant treatment of adult patients with early stage NSCLC and EGFR exon 19 deletions or exon 21 L858R mutations.²Research C for DE and. FDA. Published online December 18, 2020.

The phase 3 randomised double-blind controlled ADAURA trial assessed the efficacy and safety of osimertinib compared to placebo in patients with completely resected stage IB to IIIA EGFR Ex19del or L858R mutation-positive NSCLC after adjuvant chemotherapy.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. Eligible patients were at least 18 years of age with a World Health Organisation performance status of 0 or 1, primary non-squamous NSCLC, and pathological stage IB, II or IIIA disease. Eligible patients had either received or were scheduled to receive postoperative adjuvant chemotherapy before 1:1 randomisation to either oral osimertinib 80mg QD or matching placebo.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. The primary endpoint was disease-free survival (DFS) in patients with stage II-IIIA disease, and secondary endpoints were DFS in the overall population, overall survival (OS), health-related quality of life (HRQoL), and safety.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723.

A total of 682 patients were randomised, with 339 receiving osimertinib and 343 receiving placebo.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. Baseline characteristics were well balanced between the two groups, and most patients with stage II to IIIA and a quarter of stage IB patients had received adjuvant platinum-based chemotherapy.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. The median duration of total treatment exposure to osimertinib was 22.5 months.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723.

In patients with stage II-IIIA disease, median follow-up for DFS was 22.1 months in the osimertinib group and 14.9 months in the placebo group.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. Of those patients receiving osimertinib, 90% were alive and disease-free at 24 months, compared with 44% of those receiving placebo (HR for disease recurrence or death = 0.17; 99.06% CI: 0.11-0.26; p<0.001).³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. The median DFS was not reached in the osimertinib group and was 19.6 months in the placebo group.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723.

In the overall population, 89% and 52% of patients in the osimertinib and placebo groups, respectively, were alive and disease-free at 24 months.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. The overall hazard ratio for disease recurrence or death was 0.20 (99.12% CI: 0.14-0.30; p<0.001).³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. Median DFS was not reached with osimertinib and 27.5 months in the placebo group.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. This benefit was observed consistently across all predefined subgroups, including the use and non-use of adjuvant chemotherapy.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723.

Adverse events (AEs) were reported in 98% of patients receiving osimertinib and 89% of those receiving placebo.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. In the osimertinib group, 3% of patients experienced interstitial lung disease, while this was not experienced with placebo.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723. Dose interruptions, reductions and discontinuations occurred in 24%, 9%, and 11% of osimertinib patients, respectively.³Wu Y-L et al. N Engl J Med. 2020;383(18):1711-1723.