Wu YL, et al. - Researchers used data from a phase III study (AURA3) to compare osimertinib CNS efficacy to that of platinum-pemetrexed in patients with epidermal growth factor receptor (EGFR) T790M–positive advanced non–small-cell lung cancer (NSCLC) who experienced disease progression with prior EGFR–tyrosine kinase inhibitor treatment. They found that, the CNS efficacy shown by osimertinib was superior to that demonstrated by platinum-pemetrexed in T790M-positive advanced NSCLC.

Methods

• Eligible patients ie, those with asymptomatic, stable CNS metastases were randomly assigned 2:1 to osimertinib 80 mg once daily or platinum-pemetrexed.
• Via a blinded independent central neuroradiological review, a preplanned subgroup analysis was performed involving patients with measurable and/or nonmeasurable CNS lesions on baseline brain scan.
• Only patients with one or more measurable CNS lesions were included in the CNS evaluable for response set.
• CNS objective response rate (ORR) was assessed as primary objective.

Results

• A total of 419 patients were randomly assigned to treatment, of those, measurable and/or nonmeasurable CNS lesions were present in 116, including 46 patients with measurable CNS lesions.
• At data cutoff (April 15, 2016), 70% (21 of 30; 95% CI, 51% to 85%) and 31% (5 of 16; 95% CI, 11% to 59%) were CNS ORR with osimertinib and with platinum-pemetrexed, respectively, (odds ratio, 5.13; 95% CI, 1.44 to 20.64; P=.015) in patients with one or more measurable CNS lesions; the ORR was 40% (30 of 75; 95% CI, 29% to 52%) and 17% (7 of 41; 95% CI, 7% to 32%), respectively, in patients with measurable and/or nonmeasurable CNS lesions (odds ratio, 3.24; 95% CI, 1.33 to 8.81; P=.014).
• Findings revealed that, 8.9 months (95% CI, 4.3 months to not calculable) of median CNS duration of response was observed for osimertinib and 5.7 months (95% CI, 4.4 to 5.7 months) for platinum-pemetrexed in patients with measurable and/or nonmeasurable CNS lesions; median CNS progression-free survival was 11.7 months and 5.6 months, respectively (hazard ratio, 0.32; 95% CI, 0.15 to 0.69; P=.004).