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

ost

co

ntr

ast

FLA

IR

February 2018

T1-p

ost

co

ntr

ast

FLA

IR

April 2019

T1-p

ost

co

ntr

ast

FLA

IR

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

Conclusions

Possibilità di nuovi trattamenti “target” nei tumori cerebrali

Regorafenib, Depatux-M, Larotrectinib, Vemurafenib,

Vismodegib, AG-888: risultati positivi

Checkpoint Inhibitors in HGG con MMRd?

Protocolli sperimentali per analizzare e trattare mutazioni

target più rare

giuseppe.lombardi@iov.veneto.it