EGFR mutation analysis for prospective patient selection in AURA3 phase III trial of osimertinib versus platinum-pemetrexed in patients with EGFR T790M-positive advanced non-small-cell lung cancer

Objectives: In AURA3 (NCT02151981), osimertinib treatment provided significant clinical benefit compared with platinum-pemetrexed in patients with epidermal growth factor receptor (EGFR) T790M-positive advanced non-small-cell lung cancer (NSCLC), whose tumors had progressed on previous EGFR-tyrosine kinase inhibitor therapy. This retrospective analysis investigated detection rates for T790M, common (exon 19 deletion and L858R), and rare EGFR mutations in tissue samples from the screened population of AURA3. Materials and methods: In AURA3, eligible patients were randomized 2:1 to receive oral osimertinib 80 mg once daily or intravenous platinum-pemetrexed every 3 weeks for up to six cycles. Tumor tissue samples were centrally tested for EGFR mutations using the cobas^® EGFR Mutation Test (Version 2). T790M-positive status was a key inclusion criteria. Results: A total of 820 screened patients had a valid EGFR mutation test result, of whom 452 (55%) were T790M-positive. Detection rates were similar by ethnicity (Asian versus non-Asian) for T790M (53% versus 58%) and exon 19 deletions (56% versus 63%). Conversely, the L858R rate was higher among Asian patients versus non-Asian patients (39% versus 28%; p = 0.0017). In the overall population, a higher proportion of patients had T790M detected against a background of exon 19 deletion versus L858R mutations (64% versus 47%; p < 0.0001). Rare EGFR mutations were detected in 28 (3%) patients, including G719X (2%), exon 20 insertion (1%), and S768I (<1%). Conclusion: Among AURA3 screened patients with EGFR mutation-positive advanced NSCLC, approximately half had detectable T790M in their tumor tissue, a rate unaffected by ethnicity. Results are consistent with previous reports of T790M detection rate in this patient population.