TERAPIA ADIUVANTE, TERAPIA ADIUVANTE, NEOADIUVANTE E DELLA NEOADIUVANTE E DELLA MALATTIA AVANZATA NEL MALATTIA AVANZATA NEL CARCINOMA GASTRICO CARCINOMA GASTRICO Sara Lonardi Sara Lonardi Oncologia Medica 1 Oncologia Medica 1 Istituto Oncologico Veneto Istituto Oncologico Veneto Padova Padova
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La terapia adiuvante e neoadiuvante del cancro gastrico avanzato - Gastrolearning®
Gastrolearning II modulo/10a lezione La terapia adiuvante e neoadiuvante del cancro gastrico avanzato Dott.ssa S. Lonardi - Università di Ancona
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TERAPIA ADIUVANTE, TERAPIA ADIUVANTE, NEOADIUVANTE E DELLA NEOADIUVANTE E DELLA
MALATTIA AVANZATA NEL MALATTIA AVANZATA NEL CARCINOMA GASTRICOCARCINOMA GASTRICO
Which pts should receive CT?PS 2 pts present a very poor outcome
Shitara K,Gastr Cancer Res 2009
OSTTP
Chau I, JCO 2004
PS2
Liver mets
Peritoneal mets
Alkaline Phosphatase
Overall survival by prognostic index
Which pts should receive CT?Different risk groups
Does CT improve/impair QoL?QoL and efficacy outcomesin phase III trials
Al Batran SE Cancer,2010
How we will make any progress in the treatment of advanced GC ?
5-FU monotherapy5-FU monotherapy
EOXEOX
Median overall survival in advanced gastric cancerMedian overall survival in advanced gastric cancer
5-FU + LV +Oxaliplatin (FLO)
5-FU + LV +Oxaliplatin (FLO)
Capecitabine +Cisplatin (XP)
Capecitabine +Cisplatin (XP)
SP SP
Docetaxel +Cisplatin + 5FU
Docetaxel +Cisplatin + 5FU
11.2 mo11.2 mo
10.7 mo10.7 mo
10.5 mo10.5 mo
9.2 mo9.2 mo
7.0 mo7.0 mo
8.6 mo8.6 mo
13 mo13 moX/FP+ TX/FP+ T HER2 +
16 mo16 moHER2 IHC 3+ or IHC 2+/FISH +X/FP+ TX/FP+ T
Best supportive care
Best supportive care
4.0 mo4.0 mo
Shah MA, Clin Canc Res 2011
6926
6926345
115
345115
3618
3618365
166
365166
11564
11564
488221
488221
72478110
72478110up
down
updown
7520
7520
Type 2 - normalType 1 - normal
Type 3 - normal
GC: a single tumor or an heterogeneous disease?
•GC treated uniformly, despite epidemiologic, anatomic, and histopathologic distinctions between subtypes
•Proximal non-diffuse, diffuse, and distal non-diffuse gastric cancers can be distinguished by gene signatures
Targets in advanced GC
MET
FGFR2
EGFR
HER2
PI3K/mTOR
VEGF
1stL
Study Target N 1st EP CT scheme mOS (m) ORR
TOGA HER2 594 OSCX
CX + Trastu11.1
13.8 (16.0)34.5%47.3%
LOGIC HER2 497 OSCAPEOX
CAPEOX + Lapatinib10.512.2
40%53%
AVAGAST VEGF 774 OSCX
CX + Beva10.112.1
37%46%
REAL-3 EGFR553
(76%)OS
EOCmEOC-Pani
11.38.8
42%46%
EXPAND EGFR 904 PFSCX
CX-Cetuximab10.79.4
29%30%
AMG102 MET 118PFS (phase
II)ECX
ECX-Rilotu8.9
11.1
2ndL
GRANITE mTOR 656 PFSPlacebo
Everolimuns4.345.39
2.1%4.5%
REGARD VEGFR-2 355 OSPlacebo
Ramucirumab3.85.2
2.6%3.4%
RAINBOW VEGFR-2 665 OSPaclitaxel +/-Ramucirumab
7.369.63
16%28%
RAINBOWRAINBOW
TOGATOGA
AMG102AMG102
REGARDREGARD
Target therapy in GC: results
No patient selection based on PI3K/mTOR status
Targeting PI3K/mTORGRANITE-1 Trial: OS
Ohtsu A, JCO 2013
Target therapies
• Targeting right patients with targeted agents based on good biomarker in gastric cancer is important
• To better patient selection molecular selection is needed
• More knowledge
• Better technique
• Better design of trials
• Targeting right patients with targeted agents based on good biomarker in gastric cancer is important
• To better patient selection molecular selection is needed
• More knowledge
• Better technique
• Better design of trials
Take-home messages
- CT adiuvante: si, beneficio assoluto del 7%- CT-RT adiuvante: in casi selezionati (linfadenectomia)- CT perioperatoria: si, meglio tollerata
- CT per malattia avanzata: si, prima possibile (PS 2: ?)- CT a due farmaci: si, platinum-based- CT a tre farmaci: in casi selezionati (bulky, sintomatici)- CT target: si, trastuzumab in HER2 +- CT di seconda linea: si, in pazienti a buon PS