Randomized Phase 3 Study of Osimertinib vs Platinum-Pemetrexed for Patients with EGFR T790M-Positive Advanced NSCLC After EGFR-TKI Therapy (AURA3)

Patients enrolled in AURA3 had documented progression of advanced non–small-cell lung cancer (NSCLC) following first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy. They were T790M-positive based on the cobas® EGFR Mutation Test from a tissue biopsy after progression. Patients with asymptomatic and stable central nervous system (CNS) metastases were allowed.

Patients were randomized 2:1 to osimertinib (80 mg orally QD) once daily or platinum + pemetrexed (pemetrexed 500 mg/m2 plus either cisplatin 75 mg/m2 or carboplatin AUC 5) every 3 weeks for up to 6 cycles. Pemetrexed could be continued as maintenance treatment. The primary end point was progression-free survival (PFS) by investigator assessment. Sensitivity analysis was by blinded independent central review.

A total of 419 patients were randomized (osimertinib, n = 279; platinum-pemetrexed, n = 140). Baseline characteristics were generally balanced: female (64%), Asian (65%), never smoker (68%), EGFR exon 19 deletion (66%), CNS metastases (34%).

Osimertinib significantly improved PFS compared with platinum-pemetrexed (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.23-0.41). Median PFS was 10.1 months and 4.4 months, respectively. Overall response rate was significantly improved with osimertinib versus platinum-pemetrexed: 71% versus 31%, respectively (P <0.001). Median duration of response was 9.7 months (95% CI, 8.3-11.6 months) with osimertinib compared with 4.1 months (95% CI, 3.0-5.6 months) for platinum-pemetrexed.

Grade 3 or higher causally related adverse events (AEs) were noted in 6% of patients treated with osimertinib and 34% of patients treated with platinum-pemetrexed. The most common causally related AEs among osimertinib recipients included diarrhea (29% [grade ≥3, 1%]) and rash (28% [<1%]). In the platinum-pemetrexed group, the most common causally related AEs were nausea (47% [3%]) and decreased appetite (32% [3%]).

In patients with EGFR T790M-positive advanced NSCLC following progression on EGFR-TKI treatment, osimertinib demonstrated superior efficacy compared with platinum-pemetrexed. Risk of disease progression was reduced by 70% and the safety profile was acceptable, suggesting a new standard of care for these patients.

Papadimitrakopoulou V, et al. WCLC 2016. Abstract PL 03.03. ID 4452.

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