Mario Scartozzi Oncologia Medica Università degli Studi...
Transcript of Mario Scartozzi Oncologia Medica Università degli Studi...
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Mario Scartozzi
Oncologia Medica
Università degli Studi
Azienda Ospedaliero-Universitaria
Cagliari
Novità e Sequenze Terapeutiche nelle
Neoplasie del Tratto Gastro-Enterico
STOMACO
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Main Perioperative chemotherapy trials
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Cunningham D at ASCO 2015
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Peri-operative: FLOT VS. ECX/ECF
Al Batran SE et Al, ASCO 2017
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Peri-operative: FLOT VS. ECX/ECF
Al Batran SE et Al, ESMO 2017
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Peri-operative: FLOT VS. ECX/ECF
Al Batran SE et Al, ESMO 2017
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Peri-operative: FLOT VS. ECX/ECF
HISTOPATHOLOGY
Al Batran SE et Al, ASCO 2017
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Toxicity Profile
Al Batran SE et Al, ASCO 2017
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Al Batran SE et Al, ASCO 2017
Peri-operative: FLOT VS. ECX/ECF
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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
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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
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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
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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
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www.herceptin.com\hcp\treatment\gastric\studies\html,
The ToGA TRIAL: Updated Results (2012)
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Thuss-Patience et Al, Lancet Oncol 2017
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Tabernero et Al, ESMO 2017
Trastuzumab/Chemotherapy/Pertuzumab vs.
Trastuzumab/Chemotherapy/Placebo (JACOB Trial)
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Cunningham D et Al, NEJM 2010
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Mohammad et Al Cancer Metastasis Rev 2015
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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
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Chau I et Al, JCO 2009
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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)
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Second-line MATTERS!
Puzzoni M et Al, Transl Cancer Res 2016
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Fanotto V et Al, Gastric Cancer 2017
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Fanotto V et Al, The Oncologist 2017
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Puzzoni M et Al, Targeted Oncology 2016
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Prior CT lines
≤1: 23.1%
≥2: 66.7%
Bang et Al, ASCO 2015
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ATTRACTION-2
(Nivolumab, pre-treated, unselected, Asian)
Boku et Al, ESMO 2017
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Janjigian et Al, ASCO 2017
Checkmate 032 EG Cohort
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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
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Garattini SK et Al, WJGO 2017
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Giampieri R et Al, Gastric Cancer 2016
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Immunological effects of anticancer therapy
Galluzzi et Al, Cancer Immunology Res 2016
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