Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer

TS Mok, Y-L Wu, Myung Ju Ahn, Marina Chiara Garassino, HR Kim, SS Ramalingham, FA Shepherd, Y He, H Akamatsu, W Theelen, CK Lee, M Sebastian, A Templeton, H Mann, M Marotti, S Ghiorghiu, VA Papadimitrakopoulou, T John, A Hasani, C LeeR Dear, K O'Byrne, P Wheatley-Price, F Shepherd, Q Chu, J Laskin, N Blais, W Morzycki, Q Zhou, L Zhang, J Wang, C Zhou, S Lu, B Han, J Zhou, Y Cheng, X Zhou, W Zhang, G Chen, Y Shi, Y He, C Zhuang, Y Zhao, L Shan, L Jiang, K Li, J Cadranel, P Merle, E Quoix, D Planchard, F Barlesi, E Dansin, J Mazieres, B Coudert, M Schuler, B Deschler-Baier, F Griesinger, C Schulz, M Sebastian, M Kimmich, T Mok, J Ho, OSH Chan, VHF Lee, YC Li, G Ostoros, A Delmonte, S Novello, G Tonini, M Garassino, C Gridelli, N Ikeda, H Sakai, A Sekine, T Takahashi, Y Fujisaka, H Akamatsu, H Yoshioka, T Shimokawaji, H Tanaka, T Hida, K Kasahara, F Imamura, S Atagi, K Takeda, N Katakami, M Satouchi, N Nogami, I Okamoto, R Koyama, K Nakagawa, T Yokoi, K Kiura, M Maemondo, S Murakami, YH Kim, J Alatorre Alexander, C Hernández Hernández, W Engelsman-Theelen, A de Langen, H Groen, I Bulavina, A Poltoratskiy, K Laktionov, G Statsenko, SO South, M-J Ahn, JH Kang, JS Lee, HR Kim, JY Han, S-W Kim, EK Cho, YJ Min, KH Lee, J-H Choi, G-W Lee, SS Lee, J-S Kim, E Felip Font, D Isla Casado, J Corral Jaime, S Ponce Aix, P Garrido-Lopez, M Cobo Dols, R Ohman, B Bergman, K-G Kolbeck, C-H Yang, W-C Su, T-C Hsia, C-M Tsai, G-C Chang, C-T Yang, C-C Wang, M-L Ho, R-S Lai, Y-F Wei, J-C Ko, Fiona Blackhall, A Dangoor, P Koh, N Steele, A Price, M Nicolson, H-T Arkenau, T Newsom-Davis, V Potter, A Greystoke, N Brown, K Gold, N Rizvi, S Ramalingham, S-H Ou, T Cosgriff, R Frank, N Hanna, K Dragnev, T Mekhail, S Menon, V Charu, F Kaye, J Wrangle, F Smith, A Agrawal, I Anderson, R Hirsch, N Gill, M Harris, X Sui, C Belani

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Abstract

Background Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown. Methods In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed. In all the patients, disease had progressed during receipt of first-line EGFR-TKI therapy. The primary end point was investigator-assessed progression-free survival. Results The median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; hazard ratio; 0.30; 95% confidence interval [CI], 0.23 to 0.41; P<0.001). The objective response rate was significantly better with osimertinib (71%; 95% CI, 65 to 76) than with platinum therapy plus pemetrexed (31%; 95% CI, 24 to 40) (odds ratio for objective response, 5.39; 95% CI, 3.47 to 8.48; P<0.001). Among 144 patients with metastases to the central nervous system (CNS), the median duration of progression-free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; hazard ratio, 0.32; 95% CI, 0.21 to 0.49). The proportion of patients with adverse events of grade 3 or higher was lower with osimertinib (23%) than with platinum therapy plus pemetrexed (47%). Conclusions Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non-small-cell lung cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy. (Funded by AstraZeneca; AURA3 ClinicalTrials.gov number, NCT02151981 .)
Original languageEnglish
Pages (from-to)629-640
JournalThe New England Journal of Medicine
Volume376
Issue number7
DOIs
Publication statusPublished - 16 Feb 2017

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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