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%

--------------------------------

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