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Osimertinib plus platinum–pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study
BACKGROUND: The phase III FLAURA2 (NCT04035486) study will evaluate efficacy and safety of first-line osimertinib with platinum–pemetrexed chemotherapy versus osimertinib monotherapy in epidermal growth factor receptor mutation-positive (EGFRm) advanced/metastatic non-small-cell lung cancer (NSCLC)....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453202/ https://www.ncbi.nlm.nih.gov/pubmed/34543864 http://dx.doi.org/10.1016/j.esmoop.2021.100271 |
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author | Planchard, D. Feng, P.-H. Karaseva, N. Kim, S.-W. Kim, T.M. Lee, C.K. Poltoratskiy, A. Yanagitani, N. Marshall, R. Huang, X. Howarth, P. Jänne, P.A. Kobayashi, K. |
author_facet | Planchard, D. Feng, P.-H. Karaseva, N. Kim, S.-W. Kim, T.M. Lee, C.K. Poltoratskiy, A. Yanagitani, N. Marshall, R. Huang, X. Howarth, P. Jänne, P.A. Kobayashi, K. |
author_sort | Planchard, D. |
collection | PubMed |
description | BACKGROUND: The phase III FLAURA2 (NCT04035486) study will evaluate efficacy and safety of first-line osimertinib with platinum–pemetrexed chemotherapy versus osimertinib monotherapy in epidermal growth factor receptor mutation-positive (EGFRm) advanced/metastatic non-small-cell lung cancer (NSCLC). The safety run-in, reported here, assessed the safety and tolerability of osimertinib with chemotherapy prior to the randomized phase III evaluation. PATIENTS AND METHODS: Patients (≥18 years; Japan: ≥20 years) with EGFRm locally advanced/metastatic NSCLC received oral osimertinib 80 mg once daily (QD), with either intravenous (IV) cisplatin 75 mg/m(2) or IV carboplatin target area under the curve 5, plus pemetrexed 500 mg/m(2) every 3 weeks (Q3W) for four cycles. Maintenance was osimertinib 80 mg QD with pemetrexed 500 mg/m(2) Q3W until progression/discontinuation. The primary objective was to evaluate safety and tolerability of the osimertinib–chemotherapy combination. RESULTS: Thirty patients (15 per group) received treatment [Asian, 73%; female, 63%; median age (range) 61 (45-84) years]. Adverse events (AEs) were reported by 27 patients (90%): osimertinib–carboplatin–pemetrexed, 100%; osimertinib–cisplatin–pemetrexed, 80%. Most common AEs were constipation (60%) with osimertinib–carboplatin–pemetrexed and nausea (60%) with osimertinib–cisplatin–pemetrexed. In both groups, 20% of patients reported serious AEs. No specific pattern of AEs leading to dose modifications/discontinuations was observed; one patient discontinued all study treatments including osimertinib due to pneumonitis (study-specific discontinuation criterion). Hematologic toxicities were as expected and manageable. CONCLUSIONS: Osimertinib–chemotherapy combination had a manageable safety and tolerability profile in EGFRm advanced/metastatic NSCLC, supporting further assessment in the FLAURA2 randomized phase. |
format | Online Article Text |
id | pubmed-8453202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84532022021-09-27 Osimertinib plus platinum–pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study Planchard, D. Feng, P.-H. Karaseva, N. Kim, S.-W. Kim, T.M. Lee, C.K. Poltoratskiy, A. Yanagitani, N. Marshall, R. Huang, X. Howarth, P. Jänne, P.A. Kobayashi, K. ESMO Open Original Research BACKGROUND: The phase III FLAURA2 (NCT04035486) study will evaluate efficacy and safety of first-line osimertinib with platinum–pemetrexed chemotherapy versus osimertinib monotherapy in epidermal growth factor receptor mutation-positive (EGFRm) advanced/metastatic non-small-cell lung cancer (NSCLC). The safety run-in, reported here, assessed the safety and tolerability of osimertinib with chemotherapy prior to the randomized phase III evaluation. PATIENTS AND METHODS: Patients (≥18 years; Japan: ≥20 years) with EGFRm locally advanced/metastatic NSCLC received oral osimertinib 80 mg once daily (QD), with either intravenous (IV) cisplatin 75 mg/m(2) or IV carboplatin target area under the curve 5, plus pemetrexed 500 mg/m(2) every 3 weeks (Q3W) for four cycles. Maintenance was osimertinib 80 mg QD with pemetrexed 500 mg/m(2) Q3W until progression/discontinuation. The primary objective was to evaluate safety and tolerability of the osimertinib–chemotherapy combination. RESULTS: Thirty patients (15 per group) received treatment [Asian, 73%; female, 63%; median age (range) 61 (45-84) years]. Adverse events (AEs) were reported by 27 patients (90%): osimertinib–carboplatin–pemetrexed, 100%; osimertinib–cisplatin–pemetrexed, 80%. Most common AEs were constipation (60%) with osimertinib–carboplatin–pemetrexed and nausea (60%) with osimertinib–cisplatin–pemetrexed. In both groups, 20% of patients reported serious AEs. No specific pattern of AEs leading to dose modifications/discontinuations was observed; one patient discontinued all study treatments including osimertinib due to pneumonitis (study-specific discontinuation criterion). Hematologic toxicities were as expected and manageable. CONCLUSIONS: Osimertinib–chemotherapy combination had a manageable safety and tolerability profile in EGFRm advanced/metastatic NSCLC, supporting further assessment in the FLAURA2 randomized phase. Elsevier 2021-09-17 /pmc/articles/PMC8453202/ /pubmed/34543864 http://dx.doi.org/10.1016/j.esmoop.2021.100271 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Research Planchard, D. Feng, P.-H. Karaseva, N. Kim, S.-W. Kim, T.M. Lee, C.K. Poltoratskiy, A. Yanagitani, N. Marshall, R. Huang, X. Howarth, P. Jänne, P.A. Kobayashi, K. Osimertinib plus platinum–pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study |
title | Osimertinib plus platinum–pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study |
title_full | Osimertinib plus platinum–pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study |
title_fullStr | Osimertinib plus platinum–pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study |
title_full_unstemmed | Osimertinib plus platinum–pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study |
title_short | Osimertinib plus platinum–pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study |
title_sort | osimertinib plus platinum–pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the flaura2 study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453202/ https://www.ncbi.nlm.nih.gov/pubmed/34543864 http://dx.doi.org/10.1016/j.esmoop.2021.100271 |
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