(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
My Conflict of Interest United We Should Stand
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
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: 15-22 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 4
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: 1715-21 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 5
Perioperative Chemotherapy UK MAGIC 2006 5-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
Perioperative Chemotherapy France FNCLCC 2011 Cisplatin/5-FU No Chemo 5-y-OS 38% 24% Ychou et al. J Clin Oncol 2011; 29: 1715-21 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 7
Epirubicine or no Epirubicine? That is the Question University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 8
OE5 Study - Cunningham et al. ASCO 2015; #4002 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 9
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
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
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: 1715-21 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 12
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
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
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
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: 2068-34 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 16
FLOT-4-Study Pauligk et al. ASCO 2015; #4016 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 17
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 5,8 20 15,6.015 SR 23 16,8 27 21,1 CR+SR 31 22,6 47 36,7.015 PR 28 20,4 23 18,0 MR 44 32,1 45 35,2 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
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 probably @ ECC 09/2016 Okines et al. Annals of Oncology 2013; 24: 702 709 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 19
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. 11.8 months (HR=0.65; 95%CI 0.51-0.83) Bang Y et al. Lancet 2010; 376: 687-697 University Cancer Center Leipzig (UCCL): Prof. Dr. Florian Lordick 20
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
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
Warm regards from Leipzig, Europe!