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Disclosure Information Relationships Relevant to this Session

Maria Di Bartolomeo Nordic Pharma Please note, all disclosures are reported as submitted to ASCO, and are always available at chicago2012.asco.org. Disclosure Information Relationships Relevant to this Session.

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Disclosure Information Relationships Relevant to this Session

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  1. Maria Di Bartolomeo Nordic Pharma Please note, all disclosures are reported as submitted to ASCO, and are always available at chicago2012.asco.org Disclosure InformationRelationships Relevant to this Session

  2. ITACA-SIntergroupTrial of AdjuvantChemotherapyin Adenocarcinoma of the Stomach Comparison of a sequential treatment with irinotecan (CPT-11) plus 5-fluorouracil (5-FU)/folinic acid (LV) followed by docetaxel and cisplatinversus a 5-FU/LV regimenaspostoperative treatment for radicallyresectedgastriccancer E.Bajetta, I.Floriani, M.DiBartolomeo, R.Labianca, A.Santoro, R.Casaretti, E.Pasquini, F.Di Fabio, G.Pinotti, P.Bidoli, G.Rosati, A.Mambrini, A.Ciarlo, S.Ricci, L. Frassinetti, F.Di Costanzo, AM.Bochicchio on behalf of ITACA-S group PRESENTED BY MARIA DI BARTOLOMEO

  3. The standard recommendation for resectable gastric cancer was surgery (D1 dissection) • Meta-analysis of literature data showed a small but significant benefit with chemotherapy1 • Large, patient-level meta-analysis2 confirmed that 5-FU-based chemotherapy is associated with a statistically significant benefit: OS HR 0.82 (95% CI 0.76-0.90; P< .001) DFS HR 0.82 (95% CI 0.75-0.90; P< .001) • Our choice of 5-FU/LV regimen as control arm was based on the results of meta-analysis of randomized clinical trials Background (1 Mari, Ann Oncol,2000; 2GASTRIC, JAMA 2010) ITACA-S

  4. Italiancontribution ITACA-S

  5. FOLFIRI -> less hematological, renal and neurological toxicity and less stomatitis than cisplatin combinations • Docetaxel (TXT), CDDP and 5-FU regimen is active in terms of objective response and OS, but several grade 3-4 AEs • Treatment sequence FOLFIRI TXT/CDDP • Minimize AEs by considering each drug toxicity profile • Feasibility of the sequence was documented in the ITMO trial2 • Could more active drugs improve the benefit of FU/LV chemotherapy in patients radically resected with extended lymph nodes dissection? RationaleforExperimentalarm (1 Di Bartolomeo, Oncology 2006;) ITACA-S

  6. Study Design Independent, notfor profit, multicenter, randomized, superiority trial • Controlarm • 5-FU:400-600mg/m2d1,2-14 • LV:100mg/m2d1,2-14 • 9 cycles Randomization Adenocarcinoma of the stomach or GEJ CPT-11:180mg/m2d1-14 5-FU:400/600mg/m2d1,2-14 LV:100mg/m2d1,2-14 Experimentalarm TXT:75mg/m2d1-21 CDDP:75mg/m2d1-21 Q2wks, 4 administrations 4 cycles 3 cycles Stratification for: Center Lymph-node involvement (N-/N+) ITACA-S

  7. Histologically proven carcinoma of the stomach or gastroesophageal junction • Total/subtotal gastrectomy with at least D1 dissection (D2 recommended ) • pN+ or pT2b-3-4 • No previous radiation and/or chemotherapy • Complete recovery from surgery. The first infusion administered 3 to 8 weeks after surgery Eligibility criteria ITACA-S

  8. Primaryendpoint: Disease-FreeSurvival (DFS) • 636 events (1100 patients) required: • todetect a 20% relative reductionofrecurrence/death (HR 0.80) • assuming 3-year DFS in controlarmtobe 50% • toprovide 80% power • with 5% two-sidedsignificancelevel • Interim analysesformonitoringstudyconduction Statisticalconsiderations ITACA-S

  9. 1106 Randomized 541 control arm 565 experimental arm Feb/2005-Aug/2009 • 6 excluded for major violations: • 3 control arm • 3 experimental arm 1100 ITT population 538 control arm 562 experimental arm • 6 crossed group • 4 control-> experimental • 2 experimental -> control • 28 never started treatment: • 16 control arm • 12 experimental arm Recruitment • 1072 Safety population • 520control arm • 552 experimental arm ITACA-S

  10. Baselinecharacteristics ITACA-S

  11. Surgical report ITACA-S

  12. TNM stage ITACA-S

  13. Treatment compliance Experimental arm Control arm • Completed: 76% • - per protocol: 17% • - modified: 59% • Discontinued: 24% • - Adverseevents 15% • - Death 1% • - Withdrawal 7% • - Progressive disease 1% • Completed: 86% • - per protocol: 36% • - modified: 50% • Discontinued: 14% • - Adverseevents 6% • - Death 1% • - Withdrawal 4% • - Progressive disease 3% ITACA-S

  14. Treatment received CDDP +TXT FOLFIRI ITACA-S

  15. * * * * Grade 3-4 hematologicaltoxicity *All p<0.001 ITACA-S

  16. * * * * * Grade 3-4 non hematologicaltoxicity *All p<0.001 ITACA-S

  17. medianfollow up: 48 mos (range IQ35.5-62.2) Events and Relapses **% calculated on the total ofrelapses ITACA-S

  18. 1,0 HR:0.98 95%CI: 0.83-1.16 p=0.83 Median DFS: 41.3 months 0,8 0,6 Disease Free Survival 0,4 5-year DFS: 44.8% 0,2 Events275283 Totals538562 Control Experimental Disease-freesurvival 0,0 0 10 20 30 40 50 60 Months from randomization Patients at risk Control 538 418 328 273 194 127 71 Experimental 562 438 347 270 201 129 74 ITACA-S

  19. 1,0 HR:1.0 95%CI: 0.83-1.20 p=0.986 Median OS: 69.8 months 0,8 0,6 OverallSurvival 5-year OS: 52.2% 0,4 0,2 Events218222 Totals538562 Control Experimental Overallsurvival 0,0 0 10 20 30 40 50 60 Months from randomization Patients at risk Control 538 477 401 321 222 149 79 Experimental 562 492 404 328 230 149 81 ITACA-S

  20. HazardRatiofordeaths Test forinteraction Test forinteraction p=0.371 p=0.371 p=0.602 p=0.733 p=0.928 ITACA-S

  21. ITACA-S is the largest western trial to compare two different types of adjuvant chemotherapy in gastric cancer • Patients received adequate surgery and D2 dissection in more than 75% • Sequential irinotecan/FU-CDDP/TXT is feasible in the adjuvant setting. Howeveritis: - not more effectivethan FU/LV - more toxicthan FU/LV • According to these results there is no indication to use polychemotherapy regimen in adjuvant setting for any stage of gastric cancer Conclusions ITACA-S

  22. Financial Supportby: SanofiAventis-Italy & Pfizer- Italy ITACA-S

  23. Thanksto: ITMO GISCAD GONO SICOG Labianca, Bergamo Bidoli, Monza Foa, Milano Aitini, Mantova Barni, Treviglio Giordano, Como Martignoni, Milano Catalano, Pesaro Zaniboni, Brescia Aglietta, Candiolo Piazza, Milano Beretta, Brescia Menichetti, Senigallia Cortesi, Roma Silva, Fabriano Nardi, Reggio Calabria Cascinu, Ancona Luporini, Milano Ficarella, Urbino Falcone, Livorno Cantore, Carrara Di Leo, Prato Ricci, Pisa Magnanini, Arezzo Sozzi, Biella Fea, Cuneo Chiara, Genova Alabiso, Novara Fioretto, Antella Decensi, Genova Ciuffreda, Torino Barsani, lucca Casaretti, Napoli Farris, Sassari Filippelli, Paola Graco, Lamezia Terme Roselli , Roma Natale, Penne Buzzi, Terni Tafuto, Pozzuoli Masullo, Vallo della Lucania Bajetta, Milano Pinotti, Varese Rosati, Potenza Bordonaro, Catania Bochicchio, Rionero Fazio, Milano Marini, Brescia Buscarino,Catania Massidda, Cagliari Isa, Gorgonzola Bartolini, Sondrio Reguzzoni, Busto Arsizio Iop, Latisana Villa, Milano Ucci, Lecco Tumolo, Pordenone Frustaci, Aviano Lombardo, Pescara Sbalzarini, Casalpusterlengo Verusio, Saronno Bonetti, Legnago Monfadini, Padova Agostara, Palermo Bonciarelli, Este Marchetti, Roma Zagonel, Roma Cicero, Castrovillari Mantovani, Cagliari Duro, Como Oliani, Montecchio Maggiore Porcile, Alba Bobbio Pallavicini, Crema Gebbia, Palermo Repetto, Roma IRST Ravaioli, Rimini Amadori, Forlì Marangolo, Ravenna Gambi, Faenza Cruciani, Lugo GOCCI Fiorentini, Empoli Mazzanti, Firenze Fiorentini, Empoli Mazzanti, Firenze GIRCG APRIC Nitti, Padova Tiberio, Brescia De Manzoni, Verona GOIRC Montesarchio, Napoli Daniele, Benevento Genua, Ariano Irpino Santoro, Rozzano Boni, Reggio Emilia Di Costanzo, Firenze Cavanna, Piacenza Mattioli, Fano Pucci, Parma Bravi, Città di Castello Artioli, Carpi Passalacqua, Cremona Contu, Sassari Rossetti, Marsciano ONCOTECH GOAM De Placido, Napoli Cartenì, Napoli Martoni, Bologna Brandes, Bologna Lelli, Ferrara ……..the patients and theirfamilies ITACA-S

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