CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer

Thanyanan Reungwetwattana, Kazuhiko Nakagawa, Byoung Chul Cho, Manuel Cobo, Eun Kyung Cho, Alessandro Bertolini, Sabine Bohnet, Caicun Zhou, Ki Hyeong Lee, Naoyuki Nogami, Isamu Okamoto, Natasha Leighl, Rachel Hodge, Astrid McKeown, Andrew P. Brown, Yuri Rukazenkov, Suresh S. Ramalingam, Johan Vansteenkiste

研究成果: ジャーナルへの寄稿学術誌査読

321 被引用数 (Scopus)

抄録

Purpose We report CNS efficacy of osimertinib versus standard epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with untreated EGFR-mutated advanced non-small-cell lung cancer from the phase III FLAURA study. Patients and Methods Patients (N = 556) were randomly assigned to osimertinib or standard EGFR-TKIs (gefitinib or erlotinib); brain scans were not mandated unless clinically indicated. Patients with asymptomatic or stable CNS metastases were included. In patients with symptomatic CNS metastases, neurologic status was required to be stable for ≥ 2 weeks after completion of definitive therapy and corticosteroids. A preplanned subgroup analysis with CNS progression-free survival as primary objective was conducted in patients with measurable and/or nonmeasurable CNS lesions on baseline brain scan by blinded independent central neuroradiologic review. The CNS evaluable-for-response set included patients with ≥ one measurable CNS lesion. Results Of 200 patients with available brain scans at baseline, 128 (osimertinib, n = 61; standard EGFR-TKIs, n = 67) had measurable and/or nonmeasurable CNS lesions, including 41 patients (osimertinib, n = 22; standard EGFR-TKIs, n = 19) with ≥ one measurable CNS lesion. Median CNS progression-free survival in patients with measurable and/or nonmeasurable CNS lesions was not reached with osimertinib (95% CI, 16.5 months to not calculable) and 13.9 months (95% CI, 8.3 months to not calculable) with standard EGFR-TKIs (hazard ratio, 0.48; 95% CI, 0.26 to 0.86; P = .014 [nominally statistically significant]). CNS objective response rates were 91% and 68% in patients with $ one measurable CNS lesion (odds ratio, 4.6; 95% CI, 0.9 to 34.9; P = .066) and 66% and 43% in patients with measurable and/or nonmeasurable CNS lesions (odds ratio, 2.5; 95% CI, 1.2 to 5.2; P = .011) treated with osimertinib and standard EGFR-TKIs, respectively. Probability of experiencing a CNS progression event was consistently lower with osimertinib versus standard EGFR-TKIs. Conclusion Osimertinib has CNS efficacy in patients with untreated EGFR-mutated non-small-cell lung cancer. These results suggest a reduced risk of CNS progression with osimertinib versus standard EGFRTKIs.

本文言語英語
ページ(範囲)3290-3297
ページ数8
ジャーナルJournal of Clinical Oncology
36
33
DOI
出版ステータス出版済み - 11月 20 2018

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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