MBBS Enrichment Year 2018-19

Effectiveness of BRAF Inhibitors in Patients with BRAF-V600 Mutation-Positive Glioma: a Systematic Review Mr. Yao Ian Yuan 1,2 , Miss Sarah Dawson 1 , Professor Julian PT Higgins 1 , Mr. Luke McGuinness 1 , Dr. Alexandra McAleenan 1 , Dr. Kathreena M. Kurian 1,2 Bristol Medical School, University of Bristol 1 , Brain Tumor Research Centre, University of Bristol 2 ianyao513@gmail.com Introduction • Gliomas have a global age-adjusted incidence rate of 4.67-5.73/100,000, and a five-year survival rate of 19% (1) • Current treatment options are ineffective: diffuse gliomas are surgically challenging to remove, radiotherapy and chemotherapy have severe adverse effects • BRAF (v-RAF murine sarcoma oncogene homologue B1) inhibitors have shown to be effective for treating stage III/IV unresectable metastatic melanoma patients (2) • Effectiveness of BRAF inhibitors for BRAF-V600 mutation-positive glioma patients to increase progression-free survival (PFS) and overall survival (OS) Methods • Studies were identified from the MEDLINE and Embase databases • Data collection was done on patient demographics, tumour conditions, treatment characteristics, and primary outcomes (PFS and OS) • Kaplan–Meier analysis was done by tumour subtypes (2016 WHO Classification) and by age (paediatric ≤18 years) Figure 1 Process of identification of eligible studies. Results • 287 patients from 71 unique studies, for 171 patients with age reported the median age is 14 years-old • For 183 patients with specific diagnosis the most common ones were pilocytic astrocytoma (23.50%), ganglioglioma (20.22%), pleomorphic xanthoastrocytoma (14.75%), and glioblastoma (12.57%) • For 122 patients with best tumour response reported, 7.38% achieved complete response, 40.98% achieved partial response, 31.97% achieved stable disease, and 17.21% achieved progressive disease • The infographics below show the summary of survival for 226 patients with duration of treatment reported • High-grade tumours have a lower PFS (15 months) compared to low-grade tumours (35 months) • van Linde et al. (3) reported 299 recurrent glioblastoma multiforme patients with a median PFS of 4.3 months (systemic treatment), 7.7 months (re-irradiation), and 9.0 months (surgical reintervention), which were lower than the median PFS of 10 months for 19 glioblastoma patients included in our study Conclusions • BRAF inhibitor treatment achieves a higher PFS than conventional therapy for glioblastoma patients • Clinical effectiveness of BRAF inhibitors in patients with BRAF-V600 mutation-positive glioma could not be shown References 1. Burnet NG, Jefferies SJ, Benson RJ, Hunt DP, Treasure FP. Years of life lost (YLL) from cancer is an important measure of population burden - and should be considered when allocating research funds. British Journal of Cancer. 2005;92(2):241-5 2. Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30-9. 3. van Linde ME, Brahm CG, de Witt Hamer PC, Reijneveld JC, Bruynzeel AME, Vandertop WP, et al. Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis. J Neurooncol. 2017;135(1):183-92. 1634 records identified throughdatabase searching (Medline= 386 ,Embase=1248) 1246 records after duplicates removed Titles and abstracts assessed 1090 records excluded 156 full-text articles assessed 85 full-text articles excluded n=26 notBRAF inhibitor n=24 narrative reviews n=16 notglioma n=10 preclinical studies n=7 invitro studies n=1 notBRAFmutant n=1 repeated subjects 81publications included in this systematic review 2 additional studies fromASCO and ESMO published abstracts 8 additional studies from references on screened articles 71 studies included in analyses ◆ Time to best response ▲ PFS ✱ OS → Ongoing therapy Figure 2 Summary of survival of patients with low-grade tumours. ◆ Time to best response ▲ PFS ✱ OS → Ongoing therapy Figure 3 Summary of survival of patients with high-grade tumours. GG–ganglioglioma PA–pilocyticastrocytoma PMA–pilomyxoidastrocytoma PXA–pleomorphicxanthoastrocytoma AA–anaplasticastrocytoma AGG–anaplasticganglioglioma APXA–anaplasticpleomorphic xanthoastrocytoma GBM–glioblastoma Figure 4 Kaplan-Meier Survival Curve (PFS) for Low-Grade Tumours. Figure 5 Kaplan-Meier Survival Curve (PFS) for High-Grade Tumours. Yao Ian Yuan 195