CNS Activity of EGFR Tyrosine Kinase Inhibitor in T790M-Positive Advanced NSCLC

Key Points

  • Response rates among patients with measureable disease at baseline were 70% with osimertinib vs 31% with platinum plus pemetrexed.
  • Median CNS progression-free survival was 11.7 vs 5.6 months among all patients with CNS disease at baseline.

In a planned subgroup analysis of the phase III AURA3 trial reported in the Journal of Clinical Oncology, Wu et al found that the third-generation EGFR tyrosine kinase inhibitor osimertinib (Tagrisso) produced higher central nervous system (CNS) response rates vs platinum plus pemetrexed (Alimta) in patients with advanced EGFR T790M-positive non–small cell lung cancer (NSCLC).

In AURA3, 419 patients with disease progression on prior EGFR tyrosine kinase inhibitor treatment were randomized 2:1 to receive osimertinib at 80 mg once daily or platinum plus pemetrexed. The current subgroup analysis was conducted in patients with measurable or nonmeasurable CNS lesions on baseline brain scan by blinded independent central neuroradiologic review.

Among 419 randomized patients, 116 had measurable or nonmeasurable CNS lesions at baseline, consisting of 75 osimertinib recipients and 41 platinum-pemetrexed recipients. A total of 46 patients had measurable CNS lesions at baseline, consisting of 30 osimertinib recipients and 16 platinum-pemetrexed recipients. Among patients with measureable or nonmeasurable lesions, 68% vs 80% were Asian and 55% vs 71% were female.

CNS Responses

At data cutoff in April 2016, CNS response rates in patients with measureable lesions were 70% with osimertinib vs 31% with platinum-pemetrexed (odds ratio [OR] = 5.13, P = .015). Among patients with measureable or nonmeasurable lesions, response rates were 40% vs 17% (OR = 3.24, P = .014). Among both patients with measurable lesions and those with measureable or nonmeasurable lesions, the median duration of CNS response was 8.9 months with osimertinib vs 5.7 months with platinum-pemetrexed. Among all patients in the analysis, median CNS progression-free survival was 11.7 vs 5.6 months (hazard ratio = 0.32, P = .004).

The investigators concluded, “Osimertinib demonstrated superior CNS efficacy vs platinum-pemetrexed in T790M-positive advanced NSCLC.”

The study was supported by AstraZeneca.

Yi-Long Wu, MD, of the Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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