• Yi-Long Wu, Myung-Ju Ahn, Marina Chiara Garassino, Ji-Youn Han, Nobuyuki Katakami, Hye Ryun Kim, Rachel Hodge, Paramjit Kaur, Andrew P Brown, Dana Ghiorghiu, Vassiliki A Papadimitrakopoulou, and Mok Tony S K TSK Yi-Long Wu, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China; Myung-Ju Ahn, Sungkyunkwan University School of Medicin.
• Yi-Long Wu, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China; Myung-Ju Ahn, Sungkyunkwan University School of Medicine; Hye Ryun Kim, Yonsei University College of Medicine, Seoul; Ji-Youn Han, National Cancer Center, Goyang, Republic of Korea; Marina Chiara Garassino, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Nobuyuki Katakami, Institute of Biomedical Research and Innovation, Kobe, Japan; Rachel Hodge, Paramjit Kaur, Andrew P. Brown, and Dana Ghiorghiu, AstraZeneca, Cambridge, United Kingdom; Vassiliki A. Papadimitrakopoulou, The University of Texas MD Anderson Cancer Center, Houston, TX; and Tony S.K. Mok, Chinese University of Hong Kong, Hong Kong.
• J. Clin. Oncol. 2018 Sep 10; 36 (26): 2702-2709.

AbstractPurpose In patients with epidermal growth factor receptor ( EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC), there is an unmet need for EGFR-tyrosine kinase inhibitors with improved CNS penetration and activity against CNS metastases, either at initial diagnosis or time of progression. We report the first comparative evidence of osimertinib CNS efficacy versus platinum-pemetrexed from a phase III study (AURA3; ClinicalTrials.gov identifier: NCT02151981) in patients with EGFR T790M-positive advanced NSCLC who experience disease progression with prior EGFR-tyrosine kinase inhibitor treatment. Methods Patients with asymptomatic, stable CNS metastases were eligible for enrollment and were randomly assigned 2:1 to osimertinib 80 mg once daily or platinum-pemetrexed. A preplanned subgroup analysis was conducted in patients with measurable and/or nonmeasurable CNS lesions on baseline brain scan by blinded independent central neuroradiological review. The CNS evaluable for response set included only patients with one or more measurable CNS lesions. The primary objective for this analysis was CNS objective response rate (ORR). Results Of 419 patients randomly assigned to treatment, 116 had measurable and/or nonmeasurable CNS lesions, including 46 patients with measurable CNS lesions. At data cutoff (April 15, 2016), CNS ORR in patients with one or more measurable CNS lesions was 70% (21 of 30; 95% CI, 51% to 85%) with osimertinib and 31% (5 of 16; 95% CI, 11% to 59%) with platinum-pemetrexed (odds ratio, 5.13; 95% CI, 1.44 to 20.64; P = .015); 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). Median CNS duration of response in patients with measurable and/or nonmeasurable CNS lesions was 8.9 months (95% CI, 4.3 months to not calculable) for osimertinib and 5.7 months (95% CI, 4.4 to 5.7 months) for platinum-pemetrexed; 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). Conclusion Osimertinib demonstrated superior CNS efficacy versus platinum-pemetrexed in T790M-positive advanced NSCLC.

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