Mario Scartozzi Oncologia Medica Università degli Studi
Azienda Ospedaliero-Universitaria Cagliari
Novità nel Trattamento Del
Carcinoma Gastrico
Hananan et Al, Cell 2011
The AMG 102 Trial
High MET+ population
Iveson T et Al, ESMO 2011
Cunningham D, ASCO 2015
Cunningham D, ASCO 2015
Cunningham D, ASCO 2015
Shah M, ASCO 2015
Shah M, ASCO 2015 med OS ITT population 11.3 vs 11 (HR 0.82,p=0.24)
Kwak E et Al, Gatrointestinal Cancers Symposium 2015
Hananan et Al, Cell 2011
Lambrechts et Al, JCO 2013
Angiogenesis is an ongoing process
Aprile et Al, DRUGS 2014
Angiogenesis is an ongoing process
Fuchs et Al, Lancet Oncology 2014
The REGARD Trial
Fuchs et Al, Lancet Oncology 2014
Fuchs et Al, Lancet Oncology 2014
Adverse Events of Special Interest
Fuchs et Al, Lancet Oncology 2014
Wilke et Al, Lancet Oncology 2014
The RAINBOW Trial
RAINBOW: Overall Survival
Wilke et Al, Lancet Oncology 2014
RAINBOW: PFS
Wilke et Al, Lancet Oncology 2014
Adverse events related to chemotherapy
Wilke et Al, Lancet Oncology 2014
Hironaka S et AL ASCO 2014
Hironaka S et AL ASCO 2014
Yoon HH et AL ASCO 2014
NATURE 2014
8%
22%
20%
50%
GEJ
Pembrolizumab, a humanized highly selective IgG4 anti-PD- 1 monoclonal antibody,that directly blocks its interaction with PD-L1 and PD-L2
Encouraging results have also been seen in other
malignancies, and PD-1-
targeted therapies are likely to markedly change the
treatment landscape.
Slide Courtesy by Fernando De Vita
Bang YJ, ASCO 2015
Prior CT lines
≤1: 23.1%
≥2: 66.7%
Bang YJ, ASCO 2015
Bang YJ, ASCO 2015
Bang YJ, ASCO 2015
L
Bang YJ, ASCO 2015
L
KEYNOTE 0059
Cohort 1: pembrolizumab as third line therapy or beyond (pts enrolled regardless of PD-L1 status) Cohort 2 : pembrolizumab plus CF as first-line
therapy (pts enrolled regardless of PD-L1 status) Cohort 3: pembrolizumab monotherapy as first-line therapy ( only pts with PD-L1 positive disease)
Primary endpoint:
ORR
Secondary endpoints:
Duration of response, DCR, PFS,OS
Sharma M et Al, Science 2015
• PD-L1 IHC: Variabilità, localizzazione
subcellulare, cut-off, eterogeneità tumorale
• Espressione di PD-L1 con o senza TILs
• Espressione di PD-L1 nel tumore o nel microambiente
Slide Courtesy by Mario Mandalà
