Publication: 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
Issued Date
2018-11-20
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15277755
0732183X
0732183X
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2-s2.0-85056728302
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Clinical Oncology. Vol.36, No.33 (2018), 3290-3297
Suggested Citation
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 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. Journal of Clinical Oncology. Vol.36, No.33 (2018), 3290-3297. doi:10.1200/JCO.2018.78.3118 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/44997
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Title
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
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Other Contributor(s)
Yonsei Cancer Center
Chungbuk National University Hospital
Gachon University
Tongji University
KU Leuven– University Hospital Leuven
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Universitätsklinikum Schleswig-Holstein Campus Lübeck
National Hospital Organization, Japan
Hospital Regional Universitario Carlos Haya
Kyushu University
Ontario Cancer Institute University of Toronto
AstraZeneca
Emory University School of Medicine
Kindai University
Hospital of Sondrio
Chungbuk National University Hospital
Gachon University
Tongji University
KU Leuven– University Hospital Leuven
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Universitätsklinikum Schleswig-Holstein Campus Lübeck
National Hospital Organization, Japan
Hospital Regional Universitario Carlos Haya
Kyushu University
Ontario Cancer Institute University of Toronto
AstraZeneca
Emory University School of Medicine
Kindai University
Hospital of Sondrio
Abstract
© 2018 American Society of Clinical Oncology. 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.