Supplementary appendix

Transcription

1 Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Al-Batran S-E, Hofheinz RD, Pauligk C, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 2016; published online Oct 21.

2 Webappendix Histopathological regression after neoadjuvant 5-FU/LV, oxaliplatin and docetaxel (FLOT) versus epirubicin, cisplatin and 5-FU (ECF) in patients with resectable gastric or gastroesophageal junction adenocarcinoma: the phase II part of the randomized phase II/III FLOT4 trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Al-Batran et al. Table I: Baseline characteristics of all randomized patients ECF/ECX n=152 FLOT n=148 Total n=300 Age (years) 62 (51-68) 62 (54-69) 62 (53-69) <60 68 (45%) 65 (44%) 133 (44%) (34%) 48 (32%) 99 (33%) >70 33 (22%) 35 (24%) 68 (23%) Male 114 (75%) 117 (79%) 231 (77%) Female 38 (25%) 31 (21%) 69 (23%) ECOG performance status (68%) 93 (63%) 196 (65%) 1 48 (32%) 55 (37%) 103 (34%) (<1%) Primary tumor location Gastric 68 (45%) 73 (49%) 141 (47%) GEJ I 36 (24%) 41 (28%) 77 (26%) GEJ II 41 (27%) 27 (18%) 68 (23%) GEJ III 7 (5%) 7 (5%) 14 (5%) ct3/t4 124 (82%) 120 (81%) 244 (81%) ct1/t2 28 (18%) 27 (18%) 55 (18%) ctx (1%) 1 (<1%) cn+ 124 (82%) 113 (76%) 237 (79%) cn- 28 (18%) 35 (24%) 63 (21%) Lauren Classification Intestinal 67 (44%) 55 (37%) 122 (41%) Diffuse 43 (28%) 43 (29%) 86 (29%) Mixed 7 (5%) 11 (7%) 18 (6%) Unknown 35 (23%) 39 (26%) 74 (25%) Data are n (%) or median (IQR), unless otherwise indicated. ECOG=Eastern Cooperative Oncology Group. GEJ=gastroesophageal junction. ECF=epirubicin, cisplatin, and fluorouracil. ECX=epirubicin, cisplatin, and capecitabine. FLOT=fluorouracil, leucovorin, oxaliplatin, and docetaxel. 1

3 Figure I: Histopathological regression by treatment arm 2

4 Table II: Resection rate, R0-resection rate, and pcr as well as TRG1a/b rates in the total population of both arms pooled together by primary tumor location (intent-to-treat population) Primary location resection R0 resection pcr TRG1a/b n/n % n/n % n/n % n/n % Gastric 113/126 89,7 101/126 80,2 15/126 11,9 40/126 31,7 GEJ /139 84,2 109/139 78,4 13/139 9,4 38/139 27,3 GEJ 1 61/68 89,7 56/68 82,4 6/68 8,8 21/68 30,9 GEJ 2 49/59 83,1 46/59 78,0 7/59 11,9 15/59 25,4 GEJ 3 7/12 58,3 7/12 58,3 0/12 0,0 2/12 16,7 GEJ=gastroesophageal junction, pcr=pathological complete regression, TRG1a/b= tumor regression grade 1a/b according to Becker (pathological complete and subtotal remission) 3

5 Table III: pcr and TRG1a/b rates by primary tumor location and treatment arm (intent-to-treat population) Therapy arm / primary tumor location pcr TRG1a/b n/n % n/n % ECF/ECX (n=137) Gastric (n=59) 5/59 8,5 17/59 28,8 GEJ 1-3 (n=78) 3/78 3,8 14/78 17,9 FLOT (n=128) Gastric (n=67) 10/67 14,9 23/67 34,3 GEJ 1-3 (n=61) 10/61 16,4 24/61 39,3 GEJ=gastroesophageal junction, pcr=pathological complete regression, TRG1a/b= tumor regression grade 1a/b according to Becker (pathological complete and subtotal remission) 4

6 Table IV: Adverse event (in alphabetical order) and grade that led to treatment discontinuations in the modified ITT population of both arms (each line represents a single patient) FLOT Adverse Event CTC grade Allergic reaction 2 Fatigue 2 Infection, fever 3 Leukopenia 3 Pneumonia 3 Nausea, vomiting 3 Neurotoxic effects 3 Neurotoxic effects 2 Neurotoxic effects 2 Worsening of general condition 3 ECF/ECX Adverse Event CTC grade Fatigue 2 Renal impairment 2 Cardiac complication 3 Diarrhea 3 Diarrhea 3 Diarrhea 2 Dysphagia, pain 3 Exicosis 2 Hand-foot syndrome 2 Neutropenia 4 Leukopenia, diarrhea 4 Fatigue 3 Nausea 2 Nausea 2 Nausea, vomiting 3 Nausea, decreased appetite 2 Neurotoxic effects, mucositis, fatigue 2 Neutropenia 4 Weight decreased, fatigue 3 5

7 Table V: Sites recruiting patients into the FLOT4 trial phase II part (all Germany) Site Principal Investigator No. recruited patients phase II Krankenhaus Nordwest, Frankfurt/Main Prof. Dr. Salah-Eddin Al-Batran 24 Universitätsmedizin, Mannheim Prof. Dr. Ralf D. Hofheinz 24 Universitätsklinikum der Eberhard-Karl-Universität,Tübingen PD Dr. Hans-Georg Kopp 23 National Center for Tumor Diseases, University Hospital, Heidelberg Dr. Georg Martin Haag 20 West German Cancer Center, University Hospital, Essen Dr. Johannes Meiler 19 Universitätsklinikum Jena Dr. Udo Lindig 19 Universitätsklinikum Schleswig-Holstein, Lübeck Dr. Kim Luley 18 Klinikum Wolfsburg Prof. Nils Homann 17 Klinikum Bielefeld Dr. Stephan Probst 16 Bochum Uni Prof. Dr. Wolff Schmiegel 14 MediProjekt, Hannover Prof. Dr. Michael Koenigsmann 12 Ortenau Klinikum, Lahr Dr. Matthias Egger 10 Klinikum Ludwigsburg Prof. Dr. Karel Caca 10 Goethe University Medical Center, Frankfurt/Main Prof. Dr. Jörg Trojan 8 SLK-Kliniken GmbH, Heilbronn Prof. Dr. Uwe Martens 8 Klinikum Mutterhaus der Borromäerinnen, Trier Dr. Rolf Mahlberg 8 Augusta-Krankenanstalt, Bochum Prof. Dr. Dirk Behringer 8 University Hospital Hamburg-Eppendorf, Hamburg PD Dr. Andreas Block 7 Klinikum Aschaffenburg Prof. Dr. Wolfgang Fischbach 6 Universitätsklinikum Freiburg Dr. Katja Zirlik 6 Universitätsklinikum Dresden Dr. Gunnar Folprecht 6 Klinikum Dortmund Prof. Dr. Michael Heike 4 Horst-Schmidt-Kliniken, Wiesbaden Dr. Carmen Löhr 4 Klinikum Weiden Prof. Dr. Frank Kullmann 3 Katholisches Krankenhaus Hagen Dr. Cordula Maciejewski 2 Universitätsklinikum Kiel Prof. Dr. Dr. Michael Kneba 2 Klinikum Darmstadt Prof. Dr. Helga Bernhard 1 Gemeinschaftspraxis Dr. Weniger /Dr. Bittrich/Dr. Schütze, Erfurt Dr. Jörg Weniger 1 6

8 7