Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis

Background: In AURA3 (NCT02151981), osimertinib, a third-generation epidermal growth factor receptor (EGFR)tyrosine kinase inhibitor (TKI), significantly prolonged progression-free survival and improved response in patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC) and progression on prior EGFR-TKI treatment. We report the final AURA3 overall survival (OS) analysis. Patients and methods: Adult patients were randomized 2 : 1 to osimertinib (80 mg orally, once daily) or pemetrexed plus carboplatin/cisplatin (platinumepemetrexed) intravenously, every 3 weeks (similar to 6 cycles). Patients could crossover to osimertinib on progression confirmed by blinded independent central review. OS and safety were secondary end points. Results: A total of 279 patients were randomly assigned to receive osimertinib and 140 to platinumepemetrexed (136 received treatment). At data cut-off (DCO; 15March 2019), 188 patients (67%) receiving osimertinib versus 93 (66%) receiving platinum epemetrexed had died. The hazard ratio (HR) for OS was 0.87 [95% confidence interval (CI) 0.67-1.12; P = 0.277]; the median OS was 26.8 months (95% CI 23.5-31.5) versus 22.5 months (95% CI 20.2-28.8) for osimertinib and platinumepemetrexed, respectively. The estimated 24- and 36-month survival was 55% versus 43% and 37% versus 30%, respectively. After crossover adjustment, there was an HR of 0.54 (95% CI 0.18-1.6). Time to first subsequent therapy or death showed a clinically meaningful advantage toward osimertinib (HR 0.21, 95% CI 0.16-0.28; P < 0.001). At DCO, 99/136 (73%) patients in the platinumepemetrexed arm had crossed over to osimertinib, 66/99 (67%) of whom had died. The most common adverse events possibly related to study treatment were diarrhea (32%; grade similar to 3, 1%) and rash (grouped term; 32%; grade similar to 3, <1%) in the osimertinib arm, versus nausea (47%; grade similar to 3, 3%) in the platinumepemetrexed arm. Conclusions: In patients with T790Madvanced NSCLC, no statistically significant benefit in OS was observed for osimertinib versus platinumepemetrexed, which possibly reflects the high crossover rate of patients from platinumepemetrexed to osimertinib.