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| 001 | 163930 | ||
| 005 | 20240229123201.0 | ||
| 024 | 7 | _ | |a 10.1007/s11060-020-03640-3 |2 doi |
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| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Selt, Florian |0 P:(DE-He78)a23e88cc676489fe05be8c178ceaf58e |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Response to trametinib treatment in progressive pediatric low-grade glioma patients. |
| 260 | _ | _ | |a Dordrecht [u.a.] |c 2020 |b Springer Science + Business Media B.V |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 500 | _ | _ | |a #EA:B310#LA:B310# 2020 Sep;149(3):499-510 |
| 520 | _ | _ | |a 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.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.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%).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. |
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| 700 | 1 | _ | |a Bison, Brigitte |b 2 |
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| 773 | _ | _ | |a 10.1007/s11060-020-03640-3 |0 PERI:(DE-600)2007293-4 |n 3 |p 499-510 |t Journal of neuro-oncology |v 149 |y 2020 |x 1573-7373 |
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