Nuovi target nelle neoplasie cerebrali
Giuseppe Lombardi, MD, PhD
Dipartimento di Oncologia,Oncologia 1,
Istituto Oncologico Veneto-IRCCS Padova
Low Grade Glioma – High Risk
Stupp et al, NEJM 2005
Standard Treament for Glioblastoma
Trattamenti “personalizzati” nei tumori cerebrali?
EGFR EGFR amplified (50% GBM)
Depatuxizumab mafodotin (ABT -414)
Van den Bent et al, presented at SNO 2018
Safety
85%
Tossicità reversibile se prontamente riconosciuta: monitoraggio accurato
Reversibility of effects
Before treatment During treatment 2 months after reduction/discontinuation
Epithelium restoration
Courtesy of Dr. Parozzani Padua University
Lancet Oncology 2019
Lombardi G et al, Lancet Oncology 2019
Biomarcatore Predittivo di Efficacia?
Biomarkers for predicting survival?
Exploratory Analyses
pACC+
pACC-
Lombardi G et al. Presented at EANO 2018
Response Evaluation
May 2018
T1 -p os t con tra st FLAIR
February 2018
T1 -p o st con tra st FLAIR
April 2019
T1 -p o st con tra st FLAIR
15 months of regorafenib treatment (asthenia G2, hypertension G2)
pACC+
Checkpoint Inhibitors?
Predictive factors?
Lombardi G et al. Oral Presentation at ESMO 2018
MMR - Casistica IOV
Pembrolizumab in MMR‾ HGG – Studio osservazionale IOV
• Pembrolizumab in recurrent HGG
• ECOG PS 0-2
• MMR‾ HGG (IHC)
DC
PD
months
Istologia pazienti:
5 astrocitoma anaplastico 1 oligodendrog anaplastico 6 GBM
DCR: 33%
1 PR 3 SD
Good and prolonged response to pembrolizumab in a patient with a heavily pretreated anaplastic oligodendroglioma with MSH6-. Duration of response: 18 months
Xu et al, Trans Oncol 2018
Slide 7
Ziegler et al, BJC 2018
9 patients with primitive brain tumors reported a DCR in 100% with larotrectinib
ASCO 2019 Oral presentation 2006
JCO 2018 Xantoastrocitoma Pleomorfico 38%-100%
Ganglioglioma 18%-57%
Ganglioglioma anaplastico 50%
Astrocitoma Pilocitico 9%
High Grade Gliomas <3%
BRAF V600
IDH
ASCO 2018
Phase III study in recurrent/progressive low grade gliomas with IDH mutated
Medulloblastoma
Robinson et al, JCO 2015
