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
- PMID: 30153097
- DOI: 10.1200/JCO.2018.78.3118
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
Abstract
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 EGFR-TKIs.
Comment in
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Osimertinib Treats CNS Metastases in NSCLC.Cancer Discov. 2018 Nov;8(11):OF3. doi: 10.1158/2159-8290.CD-NB2018-121. Epub 2018 Sep 17. Cancer Discov. 2018. PMID: 30224350
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Upfront osimertinib in EGFR-mutated non-small cell lung cancer: is brain still a sanctuary?Ann Transl Med. 2018 Dec;6(Suppl 2):S110. doi: 10.21037/atm.2018.11.69. Ann Transl Med. 2018. PMID: 30740431 Free PMC article. No abstract available.
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Central nervous system activity of first-line osimertinib in epidermal growth factor receptor-mutant advanced non-small cell lung cancer.Ann Transl Med. 2019 Feb;7(3):61. doi: 10.21037/atm.2018.12.68. Ann Transl Med. 2019. PMID: 30906765 Free PMC article. No abstract available.
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Brain metastases in EGFR-positive non-small cell lung cancer: the way to the sanctuary becomes less winding.Ann Transl Med. 2019 Jul;7(Suppl 3):S80. doi: 10.21037/atm.2019.04.04. Ann Transl Med. 2019. PMID: 31576289 Free PMC article. No abstract available.
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