Research ExplorerPublicationsResponse to trametinib treatment in progressive pediatric lo...

Response to trametinib treatment in progressive pediatric low-grade glioma patients

Standard

Response to trametinib treatment in progressive pediatric low-grade glioma patients. / Selt, Florian; van Tilburg, Cornelis M; Bison, Brigitte; Sievers, Philipp; Harting, Inga; Ecker, Jonas; Pajtler, Kristian W; Sahm, Felix; Bahr, Annabelle; Simon, Michèle; Jones, David T W; Well, Lennart; Mautner, Victor-Felix; Capper, David; Hernáiz Driever, Pablo; Gnekow, Astrid; Pfister, Stefan M; Witt, Olaf; Milde, Till.

In: J NEURO-ONCOL, Vol. 149, No. 3, 09.2020, p. 499-510.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Selt, F, van Tilburg, CM, Bison, B, Sievers, P, Harting, I, Ecker, J, Pajtler, KW, Sahm, F, Bahr, A, Simon, M, Jones, DTW, Well, L, Mautner, V-F, Capper, D, Hernáiz Driever, P, Gnekow, A, Pfister, SM, Witt, O & Milde, T 2020, 'Response to trametinib treatment in progressive pediatric low-grade glioma patients', J NEURO-ONCOL, vol. 149, no. 3, pp. 499-510. https://doi.org/10.1007/s11060-020-03640-3

APA

Selt, F., van Tilburg, C. M., Bison, B., Sievers, P., Harting, I., Ecker, J., Pajtler, K. W., Sahm, F., Bahr, A., Simon, M., Jones, D. T. W., Well, L., Mautner, V-F., Capper, D., Hernáiz Driever, P., Gnekow, A., Pfister, S. M., Witt, O., & Milde, T. (2020). Response to trametinib treatment in progressive pediatric low-grade glioma patients. J NEURO-ONCOL, 149(3), 499-510. https://doi.org/10.1007/s11060-020-03640-3

Vancouver

Selt F, van Tilburg CM, Bison B, Sievers P, Harting I, Ecker J et al. Response to trametinib treatment in progressive pediatric low-grade glioma patients. J NEURO-ONCOL. 2020 Sep;149(3):499-510. https://doi.org/10.1007/s11060-020-03640-3

Bibtex

@article{1adbb6c3ce3e40ae9e80f2f607d31cc2,
title = "Response to trametinib treatment in progressive pediatric low-grade glioma patients",
abstract = "INTRODUCTION: A hallmark of pediatric low-grade glioma (pLGG) is aberrant signaling of the mitogen activated protein kinase (MAPK) pathway. Hence, inhibition of MAPK signaling using small molecule inhibitors such as MEK inhibitors (MEKi) may be a promising strategy.METHODS: In this multi-center retrospective centrally reviewed study, we analyzed 18 patients treated with the MEKi trametinib for progressive pLGG as an individual treatment decision between 2015 and 2019. We have investigated radiological response as per central radiology review, molecular classification and investigator observed toxicity.RESULTS: We observed 6 partial responses (PR), 2 minor responses (MR), and 10 stable diseases (SD) as best overall responses. Disease control rate (DCR) was 100% under therapy. Responses were observed in KIAA1549:BRAF- as well as neurofibromatosis type 1 (NF1)-driven tumors. Median treatment time was 12.5 months (range: 2 to 27 months). Progressive disease was observed in three patients after cessation of trametinib treatment within a median time of 3 (2-4) months. Therapy related adverse events occurred in 16/18 patients (89%). Eight of 18 patients (44%) experienced severe adverse events (CTCAE III and/or IV; most commonly skin rash and paronychia) requiring dose reduction in 6/18 patients (33%), and discontinuation of treatment in 2/18 patients (11%).CONCLUSIONS: Trametinib was an active and feasible treatment for progressive pLGG leading to disease control in all patients. However, treatment related toxicity interfered with treatment in individual patients, and disease control after MEKi withdrawal was not sustained in a fraction of patients. Our data support in-class efficacy of MEKi in pLGGs and necessity for upfront randomized testing of trametinib against current standard chemotherapy regimens.",
author = "Florian Selt and {van Tilburg}, {Cornelis M} and Brigitte Bison and Philipp Sievers and Inga Harting and Jonas Ecker and Pajtler, {Kristian W} and Felix Sahm and Annabelle Bahr and Mich{\`e}le Simon and Jones, {David T W} and Lennart Well and Victor-Felix Mautner and David Capper and {Hern{\'a}iz Driever}, Pablo and Astrid Gnekow and Pfister, {Stefan M} and Olaf Witt and Till Milde",
year = "2020",
month = sep,
doi = "10.1007/s11060-020-03640-3",
language = "English",
volume = "149",
pages = "499--510",
journal = "J NEURO-ONCOL",
issn = "0167-594X",
publisher = "Kluwer Academic Publishers",
number = "3",

}

RIS

TY - JOUR

T1 - Response to trametinib treatment in progressive pediatric low-grade glioma patients

AU - Selt, Florian

AU - van Tilburg, Cornelis M

AU - Bison, Brigitte

AU - Sievers, Philipp

AU - Harting, Inga

AU - Ecker, Jonas

AU - Pajtler, Kristian W

AU - Sahm, Felix

AU - Bahr, Annabelle

AU - Simon, Michèle

AU - Jones, David T W

AU - Well, Lennart

AU - Mautner, Victor-Felix

AU - Capper, David

AU - Hernáiz Driever, Pablo

AU - Gnekow, Astrid

AU - Pfister, Stefan M

AU - Witt, Olaf

AU - Milde, Till

PY - 2020/9

Y1 - 2020/9

N2 - INTRODUCTION: A hallmark of pediatric low-grade glioma (pLGG) is aberrant signaling of the mitogen activated protein kinase (MAPK) pathway. Hence, inhibition of MAPK signaling using small molecule inhibitors such as MEK inhibitors (MEKi) may be a promising strategy.METHODS: In this multi-center retrospective centrally reviewed study, we analyzed 18 patients treated with the MEKi trametinib for progressive pLGG as an individual treatment decision between 2015 and 2019. We have investigated radiological response as per central radiology review, molecular classification and investigator observed toxicity.RESULTS: We observed 6 partial responses (PR), 2 minor responses (MR), and 10 stable diseases (SD) as best overall responses. Disease control rate (DCR) was 100% under therapy. Responses were observed in KIAA1549:BRAF- as well as neurofibromatosis type 1 (NF1)-driven tumors. Median treatment time was 12.5 months (range: 2 to 27 months). Progressive disease was observed in three patients after cessation of trametinib treatment within a median time of 3 (2-4) months. Therapy related adverse events occurred in 16/18 patients (89%). Eight of 18 patients (44%) experienced severe adverse events (CTCAE III and/or IV; most commonly skin rash and paronychia) requiring dose reduction in 6/18 patients (33%), and discontinuation of treatment in 2/18 patients (11%).CONCLUSIONS: Trametinib was an active and feasible treatment for progressive pLGG leading to disease control in all patients. However, treatment related toxicity interfered with treatment in individual patients, and disease control after MEKi withdrawal was not sustained in a fraction of patients. Our data support in-class efficacy of MEKi in pLGGs and necessity for upfront randomized testing of trametinib against current standard chemotherapy regimens.

AB - INTRODUCTION: A hallmark of pediatric low-grade glioma (pLGG) is aberrant signaling of the mitogen activated protein kinase (MAPK) pathway. Hence, inhibition of MAPK signaling using small molecule inhibitors such as MEK inhibitors (MEKi) may be a promising strategy.METHODS: In this multi-center retrospective centrally reviewed study, we analyzed 18 patients treated with the MEKi trametinib for progressive pLGG as an individual treatment decision between 2015 and 2019. We have investigated radiological response as per central radiology review, molecular classification and investigator observed toxicity.RESULTS: We observed 6 partial responses (PR), 2 minor responses (MR), and 10 stable diseases (SD) as best overall responses. Disease control rate (DCR) was 100% under therapy. Responses were observed in KIAA1549:BRAF- as well as neurofibromatosis type 1 (NF1)-driven tumors. Median treatment time was 12.5 months (range: 2 to 27 months). Progressive disease was observed in three patients after cessation of trametinib treatment within a median time of 3 (2-4) months. Therapy related adverse events occurred in 16/18 patients (89%). Eight of 18 patients (44%) experienced severe adverse events (CTCAE III and/or IV; most commonly skin rash and paronychia) requiring dose reduction in 6/18 patients (33%), and discontinuation of treatment in 2/18 patients (11%).CONCLUSIONS: Trametinib was an active and feasible treatment for progressive pLGG leading to disease control in all patients. However, treatment related toxicity interfered with treatment in individual patients, and disease control after MEKi withdrawal was not sustained in a fraction of patients. Our data support in-class efficacy of MEKi in pLGGs and necessity for upfront randomized testing of trametinib against current standard chemotherapy regimens.

U2 - 10.1007/s11060-020-03640-3

DO - 10.1007/s11060-020-03640-3

M3 - SCORING: Journal article

C2 - 33026636

VL - 149

SP - 499

EP - 510

JO - J NEURO-ONCOL

JF - J NEURO-ONCOL

SN - 0167-594X

IS - 3

ER -