Mario Scartozzi Oncologia Medica Università degli Studi
Azienda Ospedaliero-Universitaria Cagliari
Novità e Sequenze Terapeutiche nelle Neoplasie del Tratto Gastro-Enterico
STOMACO
Main Perioperative chemotherapy trials
Cunningham D at ASCO 2015
Peri-operative: FLOT VS. ECX/ECF
Al Batran SE et Al, ASCO 2017
Peri-operative: FLOT VS. ECX/ECF
Al Batran SE et Al, ESMO 2017
Peri-operative: FLOT VS. ECX/ECF
Al Batran SE et Al, ESMO 2017
Peri-operative: FLOT VS. ECX/ECF HISTOPATHOLOGY
Al Batran SE et Al, ASCO 2017
Toxicity Profile
Al Batran SE et Al, ASCO 2017
Al Batran SE et Al, ASCO 2017
Peri-operative: FLOT VS. ECX/ECF
First-line FOLFIRI: efficacy
Regimen No. RR PFS OS TTF
CPT-11 + 5-FU 170 31.8% 5.0 9.0 4.0
CDDP + 5-FU 163 25.8% 4.2 8.7 3.4
P-value
10.23 0.088 HR=1.08 0.018
FOLFIRI 207 37.8% 5.8 9.7 5.1
ECF 209 39.2% 5.3 9.5 4.2
P-value
2NS 0.96 HR=1.01 0.008
1
Dank M et al. Ann Oncol 2008
2
Guimbaud R et al. J Clin Oncol 2014
5-FU vs. capecitabine and cisplatin vs. oxaliplatin
Cunningham D et al. N Engl J Med 2008
Al-Batran SE et al. J Clin Oncol 2008
Kang YK et al. Ann Oncol 2009
V325 Shah JCO 2015
GATE DCF CF DCF mDCF TE TEF TE
X RR
(%)
37 25 33 49 23 46.6 25.6
TTP 5.6 3.7 6.5 9.6 4.5 7.7 5.6
OS 9.2 8.6 12.6 18.8 9 14.6 11.3
Studio Schema Pts. RR (%)
PFS OS p
FLAGs 5FU CDDP S-1 CDDP
521 508
31.9 29.1
5.5 4.8
7.9 8.6
NS
V325 CF DCF
224 221
25 37
3.7 5.6
8.6 9.2
0.02
REAL 2 ECF EOF ECX EOX
263 245 250 244
41 42 46 48
6.2 6.5 6.7 7.0
9.9 9.3 9.9 11.2
NA
ML17032 FP XP
137 139
29 41
5.0 5.6
9.3 10.5
NS
www.herceptin.com\hcp\treatment\gastric\studies\html,
The ToGA TRIAL: Updated Results (2012)
Thuss-Patience et Al, Lancet Oncol 2017
Tabernero et Al, ESMO 2017
Trastuzumab/Chemotherapy/Pertuzumab vs.
Trastuzumab/Chemotherapy/Placebo (JACOB Trial)
Cunningham D et Al, NEJM 2010
Mohammad et Al Cancer Metastasis Rev 2015
Carcinoma Gastrico Avanzato Localmente Avanzato
Non Resecabile, M0 Metastasi a distanza
RR (Conversione/Resezione) PFS
OS QoL
OS PFS QoL
The “Make it or Break it” approach
Scelta preferibile:
Tripletta con docetaxel
The “Strategic” approach
modulazione del trattamento per
massima efficacia, contenimento del
profilo di tossicità, seconda linea
Chau I et Al, JCO 2009
Metastasi a distanza
The “Strategic” approach Doppietta/tripletta
ECOG
Metastasi Epatiche Carcinosi
ALP
Basso Rischio Platino/FU
Irinotecan/FU
Alto Rischio Tripletta
(Docetaxel) Rischio Intermedio
Doppietta/Tripletta
(Docetaxel)
Second-line MATTERS!
Puzzoni M et Al, Transl Cancer Res 2016
Fanotto V et Al, Gastric Cancer 2017
Fanotto V et Al, The Oncologist 2017
Puzzoni M et Al, Targeted Oncology 2016
Prior CT lines
≤1: 23.1%
≥2: 66.7%
Bang et Al, ASCO 2015
ATTRACTION-2
(Nivolumab, pre-treated, unselected, Asian)
Boku et Al, ESMO 2017
Janjigian et Al, ASCO 2017
Checkmate 032 EG Cohort
Fuchs et Al, ASCO 2017
KEYNOTE-059 (NCT02335411)
ORR
--- All 11.6%
--- PD-L1 pos 15.5%
PD-L1 neg 6.4%
---
Fuchs et Al, ASCO 2017
KEYNOTE-059 (NCT02335411)
Response according to MSI
Garattini SK et Al, WJGO 2017
Giampieri R et Al, Gastric Cancer 2016
Immunological effects of anticancer therapy
Galluzzi et Al, Cancer Immunology Res 2016
