The Effects of Dabrafenib And/or Trametinib Treatment in Braf V600-mutant Glioma: a Systematic Review and Meta-analysis

Overview

Journal Neurosurg Rev

Specialty Neurosurgery

Date 2024 Aug 22

PMID 39172230

Authors

Jun Lei

Yanhui Liu

Yingjun Fan

Affiliations

Soon will be listed here.

Abstract

This study aimed to evaluate the effects of dabrafenib and/or trametinib therapy in BRAF v600-mutant glioma treatment. PubMed, the Cochrane Library, EMBASE and Web of Science were searched from inception to Sep 2023. Inclusion criteria were designed based on the PICO principle to select relevant articles. Search keywords included 'dabrafenib', 'trametinib', 'glioma' and other related keywords. Outcomes included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and death events. Methodological index for non-randomized studies (MINORS) was used to assess the methodological quality. Stata 14.0 was selected to perform the Cochrane Q and I statistics to test the heterogeneity among all studies. As for publication bias assessment and sensitivity analysis, the funnel plot, Egger regression test, Begg test, and trim and fill method were selected. Including 8 studies for meta-analysis. The pooled results of the single-arm trials showed that the median PFS and median OS after treatment were 6.10 months and 22.73 months, respectively. Notably, this study found a high incidence of AEs and death events of 50% and 43% after treatment. All the above findings were statistically significant. Also, this study statistically supported the advantage of disease response improvement after the combination therapy in BRAF v600-mutant glioma patients, which were shown as a pooled rate of PR (30%), a pooled rate of CR (18%), and a pooled rate of ORR (39%). And the AE rate was lower in the monotherapy group (AE: 25%) than in the combination treatment group (AE: 60%). Sensitivity analysis indicated that all the results were robust. Based on current literature outcomes, dabrafenib and/or trametinib may lead to the median PFS of 6.10 months and median OS as 22.73 months for BRAF v600-mutant glioma patients, and the safety of monotherapy is better than that of combination therapy. This conclusion needs to be treated with caution and further verified.

Citing Articles

Efficacy and safety of dabrafenib plus trametinib in pediatric versus adult gliomas: a systematic review and meta-analysis.

Hajikarimloo B, Tos S, Sabbagh Alvani M, Kooshki A, Hasanzade A, Zare A Childs Nerv Syst. 2025; 41(1):104.

PMID: 39904910 DOI: 10.1007/s00381-025-06760-1.

Dabrafenib plus trametinib in low-grade versus high-grade gliomas: a systematic review and meta-analysis.

Hajikarimloo B, Habibi M, Kooshki A, Sabbagh Alvani M, Zare A, Hasanzade A BMC Cancer. 2024; 24(1):1473.

PMID: 39614165 PMC: 11606206. DOI: 10.1186/s12885-024-13229-y.

Letter to Editor, "The effects of dabrafenib and/or trametinib treatment in Braf V600mutant glioma: a systematic review and metaanalysis".

Chellapandian H, Jeyachandran S Neurosurg Rev. 2024; 47(1):613.

PMID: 39271502 DOI: 10.1007/s10143-024-02858-3.

References

Nicolaides T, Nazemi K, Crawford J, Kilburn L, Minturn J, Gajjar A . Phase I study of vemurafenib in children with recurrent or progressive BRAF mutant brain tumors: Pacific Pediatric Neuro-Oncology Consortium study (PNOC-002). Oncotarget. 2020; 11(21):1942-1952. PMC: 7260122. DOI: 10.18632/oncotarget.27600. View

Ho C, Mobley B, Gordish-Dressman H, VandenBussche C, Mason G, Bornhorst M . A clinicopathologic study of diencephalic pediatric low-grade gliomas with BRAF V600 mutation. Acta Neuropathol. 2015; 130(4):575-85. DOI: 10.1007/s00401-015-1467-3. View

Perez J, Muchart J, Santa-Maria Lopez V, Capella M, Salvador N, Jaume S . Targeted therapy for pediatric low-grade glioma. Childs Nerv Syst. 2021; 37(8):2511-2520. DOI: 10.1007/s00381-021-05138-3. View

Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021; 10(1):89. PMC: 8008539. DOI: 10.1186/s13643-021-01626-4. View

Schreck K, Grossman S, Pratilas C . BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors. Cancers (Basel). 2019; 11(9). PMC: 6769482. DOI: 10.3390/cancers11091262. View

Wan P, Garnett M, Roe S, Lee S, Niculescu-Duvaz D, Good V . Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell. 2004; 116(6):855-67. DOI: 10.1016/s0092-8674(04)00215-6. View

Menzies A, Long G . Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma. Clin Cancer Res. 2014; 20(8):2035-43. DOI: 10.1158/1078-0432.CCR-13-2054. View

Geurts M, van den Bent M . On high-risk, low-grade glioma: What distinguishes high from low?. Cancer. 2018; 125(2):174-176. PMC: 6587541. DOI: 10.1002/cncr.31834. View

Hauschild A, Grob J, Demidov L, Jouary T, Gutzmer R, Millward M . Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012; 380(9839):358-65. DOI: 10.1016/S0140-6736(12)60868-X. View

10.

Tan J, Wijesinghe I, Kamarudin M, Parhar I . Paediatric Gliomas: BRAF and Histone H3 as Biomarkers, Therapy and Perspective of Liquid Biopsies. Cancers (Basel). 2021; 13(4). PMC: 7913734. DOI: 10.3390/cancers13040607. View

11.

Bouffet E, Hansford J, Garre M, Hara J, Plant-Fox A, Aerts I . Dabrafenib plus Trametinib in Pediatric Glioma with V600 Mutations. N Engl J Med. 2023; 389(12):1108-1120. DOI: 10.1056/NEJMoa2303815. View

12.

Barbato M, Nashed J, Bradford D, Ren Y, Khasar S, Miller C . FDA Approval Summary: Dabrafenib in Combination with Trametinib for BRAFV600E Mutation-Positive Low-Grade Glioma. Clin Cancer Res. 2023; 30(2):263-268. PMC: 10841289. DOI: 10.1158/1078-0432.CCR-23-1503. View

13.

Tsai J, Choi J, Ouaalam H, Aguilar Murillo E, Yeo K, Vogelzang J . Integrated response analysis of pediatric low-grade gliomas during and after targeted therapy treatment. Neurooncol Adv. 2023; 5(1):vdac182. PMC: 10011805. DOI: 10.1093/noajnl/vdac182. View

14.

Bandopadhayay P, Bergthold G, London W, Goumnerova L, Morales La Madrid A, Marcus K . Long-term outcome of 4,040 children diagnosed with pediatric low-grade gliomas: an analysis of the Surveillance Epidemiology and End Results (SEER) database. Pediatr Blood Cancer. 2014; 61(7):1173-9. PMC: 4657506. DOI: 10.1002/pbc.24958. View

15.

Davidenko J, Antzelevitch C . The effects of milrinone on action potential characteristics, conduction, automaticity, and reflected reentry in isolated myocardial fibers. J Cardiovasc Pharmacol. 1985; 7(2):341-9. DOI: 10.1097/00005344-198503000-00021. View

16.

Begg C, Mazumdar M . Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50(4):1088-101. View

17.

Armstrong G, Liu Q, Yasui Y, Huang S, Ness K, Leisenring W . Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2009; 101(13):946-58. PMC: 2704230. DOI: 10.1093/jnci/djp148. View

18.

Nobre L, Zapotocky M, Ramaswamy V, Ryall S, Bennett J, Alderete D . Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition. JCO Precis Oncol. 2020; 4. PMC: 7446502. DOI: 10.1200/PO.19.00298. View

19.

Welsh S, Corrie P . Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol. 2015; 7(2):122-36. PMC: 4346212. DOI: 10.1177/1758834014566428. View

20.

Tsirogiannis P, Reissmann D, Heydecke G . Evaluation of the marginal fit of single-unit, complete-coverage ceramic restorations fabricated after digital and conventional impressions: A systematic review and meta-analysis. J Prosthet Dent. 2016; 116(3):328-335.e2. DOI: 10.1016/j.prosdent.2016.01.028. View