Cargando…

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)....

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
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
_version_ 1784570233180127232
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
work_keys_str_mv AT planchardd osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT fengph osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT karasevan osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT kimsw osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT kimtm osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT leeck osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT poltoratskiya osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT yanagitanin osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT marshallr osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT huangx osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT howarthp osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT jannepa osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study
AT kobayashik osimertinibplusplatinumpemetrexedinnewlydiagnosedepidermalgrowthfactorreceptormutationpositiveadvancedmetastaticnonsmallcelllungcancersafetyruninresultsfromtheflaura2study