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

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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 EGFRTKIs.

Original languageEnglish
Pages (from-to)3290-3297
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number33
DOIs
Publication statusPublished - Nov 20 2018

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
osimertinib
Disease-Free Survival
Brain
Odds Ratio
Neoplasm Metastasis
Nervous System
Adrenal Cortex Hormones

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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

In: Journal of Clinical Oncology, Vol. 36, No. 33, 20.11.2018, p. 3290-3297.

Research output: Contribution to journalArticle

Reungwetwattana, T, Nakagawa, K, Cho, BC, Cobo, M, Cho, EK, Bertolini, A, Bohnet, S, Zhou, C, Lee, KH, Nogami, N, Okamoto, I, Leighl, N, Hodge, R, McKeown, A, Brown, AP, Rukazenkov, Y, Ramalingam, SS & Vansteenkiste, J 2018, '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, pp. 3290-3297. https://doi.org/10.1200/JCO.2018.78.3118
Reungwetwattana, Thanyanan ; Nakagawa, Kazuhiko ; Cho, Byoung Chul ; Cobo, Manuel ; Cho, Eun Kyung ; Bertolini, Alessandro ; Bohnet, Sabine ; Zhou, Caicun ; Lee, Ki Hyeong ; Nogami, Naoyuki ; Okamoto, Isamu ; Leighl, Natasha ; Hodge, Rachel ; McKeown, Astrid ; Brown, Andrew P. ; Rukazenkov, Yuri ; Ramalingam, Suresh S. ; Vansteenkiste, Johan. / 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. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 33. pp. 3290-3297.
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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",
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 EGFRTKIs.",
author = "Thanyanan Reungwetwattana and Kazuhiko Nakagawa and Cho, {Byoung Chul} and Manuel Cobo and Cho, {Eun Kyung} and Alessandro Bertolini and Sabine Bohnet and Caicun Zhou and Lee, {Ki Hyeong} and Naoyuki Nogami and Isamu Okamoto and Natasha Leighl and Rachel Hodge and Astrid McKeown and Brown, {Andrew P.} and Yuri Rukazenkov and Ramalingam, {Suresh S.} and Johan Vansteenkiste",
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language = "English",
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TY - JOUR

T1 - 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

AU - Reungwetwattana, Thanyanan

AU - Nakagawa, Kazuhiko

AU - Cho, Byoung Chul

AU - Cobo, Manuel

AU - Cho, Eun Kyung

AU - Bertolini, Alessandro

AU - Bohnet, Sabine

AU - Zhou, Caicun

AU - Lee, Ki Hyeong

AU - Nogami, Naoyuki

AU - Okamoto, Isamu

AU - Leighl, Natasha

AU - Hodge, Rachel

AU - McKeown, Astrid

AU - Brown, Andrew P.

AU - Rukazenkov, Yuri

AU - Ramalingam, Suresh S.

AU - Vansteenkiste, Johan

PY - 2018/11/20

Y1 - 2018/11/20

N2 - 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.

AB - 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.

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U2 - 10.1200/JCO.2018.78.3118

DO - 10.1200/JCO.2018.78.3118

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JO - Journal of Clinical Oncology

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