Mario Scartozzi Oncologia Medica Università degli Studi...
Transcript of Mario Scartozzi Oncologia Medica Università degli Studi...
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-value1 0.23 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-value2 NS 0.96 HR=1.01 0.008
1Dank M et al. Ann Oncol 2008
2Guimbaud 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%
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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