(Neo-) adjuvant Treatment of Gastric Cancer. - The European View

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1 (Neo-) adjuvant Treatment of Gastric Cancer - The European View Florian Lordick, MD Professor of Oncology Director of the University Cancer Center Leipzig (UCCL) University of Leipzig, Germany

2 My Conflict of Interest United We Should Stand

3 Gastric Cancer Survival in Europe Only ~25% of European GC patients are long-term survivors De Angelis et al., Lancet Oncol 2014 Jan;15(1):23-34 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 3

4 Gastric Cancer European Standard of Care Mucosal T1a Endoscopic resection R0 R1 Observation Primary diagnosis and staging ct1 (> T1a) ct2 N0 M0 Surgery D2-or D1+ LAD ct3 / 4 or N+ Perioperative chemotherapy Radiochemo as an alternative in EG junction adenocarcinoma Lordick et al. Internist 2014; 55: University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 4

5 EU Landmark Trials Perioperative Chemotherapy MAGIC + FNCLCC CTx* Surgery CTx* Stage II/III Stomach + Cardia + Dist. Eso RANDOM Primary endpoint: survival Surgery *CTX (Chemotherapy): MAGIC, ECF (epirubicine, cisplatin, fluorouracil) FNCLCC, CF (cisplatin, fluorouracil) Cunningham D et al. N Engl J Med 2006;355:11-20 Ychou et al. J Clin Oncol 2011; 29: University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 5

6 Perioperative Chemotherapy UK MAGIC y-OS 36% (ECF) 23% (No chemo) Cunningham D et al. N Engl J Med 2006;355:11-20 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 6

7 Perioperative Chemotherapy France FNCLCC 2011 Cisplatin/5-FU No Chemo 5-y-OS 38% 24% Ychou et al. J Clin Oncol 2011; 29: University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 7

8 Epirubicine or no Epirubicine? That is the Question University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 8

9 OE5 Study - Cunningham et al. ASCO 2015; #4002 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 9

10 Should Epirubicine Retire? Stop! Don t go too fast OE-5 is a study on oesophageal / OGJ cancer MAGIC (3 x ECF Surgery 3 x ECF) remains the largest perioperative study ever done in Gastric Cancer ECF periop. remains one valid option for treating patients with locally advanced GC University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 10

11 Perioperative Chemotherapy Delivery of pre- and post-op chemotherapy MAGIC (9 wks ECF) FNCLCC (8 wks CF) Pre-op. CTX completed 86% 89% Post-op. CTX given 55% 51% Give chemo pre-op! Post-op. chemo may become difficult. Is the postop. chemotherapy really important??? Should we switch the regimen in pre-op non-responders??? University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 11

12 Perioperative Chemotherapy Location Matters UK MAGIC 2006 France FNCLCC 2011 Cunningham D et al. N Engl J Med 2006;355:11-20 Ychou et al. J Clin Oncol 2011; 29: University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 12

13 Standard of Care - Europe Clinical stages T1b+T2 N+ and/or T3/T4 resectable Neoadjuvant Radio-CTx Periop. Chemo-Tx University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 13

14 Radiotherapy and D1+/D2 Surgery in GC - Trials CRITICS (NL, Sweden) Stage Ib-IVa R CTx (ECX) Resection Radio-CTx CTx (ECX) Resection CTx (ECX) TOPGEAR (AUS, CAN, EU) Stage Ib-IVa R Radio-CTx Resection CTx (ECX) CTx (ECX) Resection CTx (ECX) University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 14

15 Integration of Novel Drugs Chemotherapy Taxanes FLOT-4 FLOT vs. ECF Phase III Anti-Angiogenesis Bevacizumab STO-3 (MAGIC-B) ECX+/-Bevacizumab Phase III Anti-Her2 Trastuzumab/ INNOVATION Pertuzumab Phase II / III University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 15

16 Do Taxanes improve the histopathologicalcomplete response rate? Pooled analysis (n=120) of neoadjuvant Docetaxel-treated patients Gastro-Tax (Munich), DCX (Berlin), FLOT (Frankfurt) pcr-rate 18/120 patients (15%) Lorenzen S. et al. Ann Oncol 2013; 24: University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 16

17 FLOT-4-Study Pauligk et al. ASCO 2015; #4016 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 17

18 FLOT-4-Study Interim Analysis (Phase 2) on ITT Population: FLOT (5FU, Leucovorin, Oxaliplatin, Docetaxel) versus ECF(X) Pathological ECF/ECX (n=137) FLOT (n=128) P value Remission no. % no. % (2-sided) CR 8 5, ,6.015 SR 23 16, ,1 CR+SR 31 22, ,7.015 PR 28 20, ,0 MR 44 32, ,2 NR 8 5,8 4 3,1 Not resectable 26 19,0 9 7,0 Pauligk et al. ASCO 2015; #4016 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 18

19 Anti-Angiogenesis STO3/MAGIC-B (UK) Stage Ib-IVa R ECC + Bev Resection ECC + Bev CTx (ECC) Resection CTx (ECC) *Chemotherapy: ECC (epirubicine, cisplatin, capecitabine) Bev (bevacizumab) Survival outcomes awaited ECC 09/2016 Okines et al. Annals of Oncology 2013; 24: University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 19

20 HER2-positive Gastric Cancer Survival gaintrastuzumab in HER2-pos. Gastric cancer StageIV Therapeutically relevant HER2 positivity: ~ 16% Trastuzumab in stage IV HER2+ gastric cancer: Survival 16.0 vs months (HR=0.65; 95%CI ) Bang Y et al. Lancet 2010; 376: University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 20

21 INNOVATION Study STAGE 1: Randomized phase II «pick-the winner» of two experimental arms 1:2:2 randomization STAGE 2: Randomized phase III with best experimental arm of STAGE 1 1:3 randomization CTX only CTX only R CTX + Trastuzumab Chemotherapy + Trastuzumab (+ Pertuzumab) CTX + Trastuzumab + Pertuzumab Global PI: Dr. AD Wagner, Lausanne IMAGE substudy in selected centers: What is the accuracy of FDG-PET in targeted (antibody) treatment University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 21

22 Summary Perioperative CTx is the standard of care in EU Indicated for stages II and III ct1b-2 N-pos.; ct3-4 (resectable) N-any Neoadjuvant Radio-CTx is an alternative option in EGJ Ongoing studies on radiation in addition to periop CTx Adjuvant CRITICS Neoadjuvant TOPGEAR New drugs are being tested Taxanes: FLOT-4 Bevacizumab: STO-3 anti-her2-directed mabs: EORTC-INNOVATION University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 22

23 Warm regards from Leipzig, Europe!