Study concept and design: Zhu, Poon, C.-L. Chen, Furuse, Anak, L.-T. Chen.
Acquisition, analysis, or interpretation of data: Zhu, Kudo, Assenat, Cattan, Kang, Lim, Poon, Blanc, Vogel, Dorval, Peck-Radosavljevic, Santoro, Daniele, Furuse, Jappe, Perraud, Anak, Sellami, L.-T. Chen.
Drafting of the manuscript: Zhu, Lim, C.-L. Chen, Jappe, Perraud, Anak, Sellami.
Critical revision of the manuscript for important intellectual content: Zhu, Kudo, Assenat, Cattan, Kang, Poon, Blanc, Vogel, Dorval, Peck-Radosavljevic, Santoro, Daniele, Furuse, Perraud, Anak, Sellami, L.-T. Chen.
Statistical analysis: Jappe, Perraud, Anak.
Administrative, technical, or material support: Zhu, Kang, Vogel, C.-L. Chen, Santoro, Furuse, Jappe.
Study supervision: Zhu, Kudo, Lim, Peck-Radosavljevic, Anak, Sellami, L.-T. Chen.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Zhu reports consultancy for sanofi-aventis, Exelixis, Eisai, and Daiichi Sankyo. Dr Kudo reports having received a grant, consulting fee or honorarium, and support for travel to meetings for the study or other purposes and consultancy for Novartis. Dr Cattan reports receiving support for travel to meetings for the study or other purposes from Novartis and consultancy for Novartis. Dr Kang reports board membership, consultancy, and grants or grants pending for Novartis. Dr Vogel reports consultancy, payment for lectures, and payment for manuscript preparation from Bayer, Celgene, and Roche; consultancy and payment for lectures from Amgen; and payment for lectures from Dr Falk Pharma. Dr Peck-Radosavljevic reports consulting fee or honorarium and support for travel to meetings for the study or other purposes from Novartis; board membership for BioAlliance Pharma; consultancy for Bayer, Gilead, Merck Sharpe Dohme, Jansen, Roche, AbbVie, Bristol-Myers Squibb, and Boehringer Ingelheim; grants or grants pending for Bayer, Abbott, and Gilead; payments for lectures including service on speakers’ bureaus for Bayer, Merck Sharpe Dohme, Roche, Eli Lilly, Bristol-Myers Squibb, and Jansen; payment for manuscript preparation for Bayer; and payment for development of educational presentation for Bayer and Gilead. Dr Daniele reports board membership for Bayer and Daiichi Sankyo, consultancy for Bayer, and payments for lectures including service on speakers’ bureaus for Bayer, Daiichi Sankyo, and Novartis. Dr Furuse reports consulting fee or honorarium from Novartis; fees for participation in review activities such as data monitoring boards, statistical analysis, end point committees, and the like from Novartis; board membership for Chugai Pharmaceutical, Taiho Pharmaceutical, Bayer Pharmaceutical, Zeria Pharmaceutical, GlaxoSmithKline, and Yakult; consultancy for GlaxoSmithKline, Zeria Pharmaceutical, Ono Pharmaceutical, and Boehringer Ingelheim; grants or grants pending from Taiho Pharmaceutical, Chugai Pharmaceutical, Pfizer, Bayer Pharmaceutical, GlaxoSmithKline, Takeda BioDevelopment Center Limited, Eli Lilly Japan, Yakult, Ono Pharmaceutical, Onco Therapy Science, and Takeda Pharmaceutical; payment for lectures including service on speakers’ bureaus for Chugai Pharmaceutical, Taiho Pharmaceutical, Bayer Pharmaceutical, Eli Lilly Japan, and Pfizer. Ms Jappe reports employment and stock/stock options for Novartis Pharma AG. Mr Perraud reports employment for Novartis Pharma AG. Dr Anak reports employment and stock/stock options for Novartis Pharma AG. Dr Sellami reports employment and stock/stock options for Novartis Pharmaceuticals Corporation. Dr L.-T. Chen reports support for travel to meetings for the study or other purposes, consultancy, grants/grants pending, and payment for lectures including service on speakers’ bureaus for Novartis. No other disclosures were reported.
Funding/Support: This study was sponsored by Novartis Pharmaceuticals. Medical writing and editorial support in the preparation of the manuscript was provided by Melanie Leiby, PhD, and Dolores Matthews, MEd, of ApotheCom (Yardley, Pennsylvania) and was supported by Novartis Pharmaceuticals.
Role of the Sponsor: Representatives of the study sponsor contributed to the design of the trial. Data were collected through the sponsor’s data management system and were analyzed by their statistical team. An independent data monitoring committee reviewed interim efficacy analyses and oversaw safety data. As authors of the manuscript, representatives of the sponsor contributed to data interpretation and writing, reviewing, and amending the manuscript and participated in the decision to submit the manuscript for publication.
Previous Presentation: These data were presented in part at the 2014 Gastrointestinal Cancers Symposium; January 16-18, 2014; San Francisco, California.
Study Steering Committee: Co-chairs: Zhu, L.-T. Chen (senior author). Members: Kang, Lim, Poon, Vogel, Daniele, Furuse, Perraud, Anak, Sellami.
Additional Contributions: We thank Ghassan Abou-Alfa, MD (Memorial Sloan-Kettering Cancer Center, New York, New York), Hironobu Minami, MD (Kobe University Hospital, Kobe, Japan), Richard S. Finn, MD (University of California, Los Angeles), and Lee-Jen Wei, PhD (Harvard School of Public Health, Boston, Massachusetts) for serving on the independent data monitoring committee (chaired by Dr Abou-Alfa) that reviewed interim efficacy analyses and oversaw safety data. These individuals were compensated. We thank the following investigators for enrolling patients in the EVOLVE-1 study: Australia: Jonathan Cebon (Ludwig Institute for Cancer Research, Heidelburg), Jacob George (Westmead Hospital, Westmead), Simone Strasser (Royal Prince Alfred Hospital, Camperdown), Amany Zekry (St George Hospital Clinical School, University of New South Wales, Sydney). Austria: Rudolf Stauber (LKH Graz Med. Universität Klinik, Graz), Wolfgang Vogel (Univ Klinik fur Innere Medizin Innsbruck, Innsbruck). Belgium: Ivan Borbath (Cliniques Universitaires Saint-Luc, Brussels), Marc Peeters (UZ Antwerpen, Edegem), Jean-Luc Van Laethem (CHU Erasme, Brussels), Chris Verslype (Gasthuisberg University Hospital, Leuven). Canada: Yoo-Joung Ko (Sunnybrook Health Sciences Center, Toronto), Walter Kocha (London Regional Cancer Cantre, London), Richard Létourneau (CHUM–Campus St Luc, Montreal), Peter Metrakos (MUHC–Royal Victoria Hospital, Montreal). China: Minshan Chen (Sun Yat-sen University Cancer Center, Guangzhou), Guohong Han (Xijing Hospital, Fourth Military Medical University, Xi’an), Hongming Pan (Sir Run Run Shaw Hospital and Zhejiang University Medical College, Zhejiang), Shukui Qin (PLA No. 81 Hospital, Nanjing), Jianming Xu (307 Hospital of the PLA, Beijing), Lvnan Yan (West China Hospital of Sichuan and University Chengdu, Sichuan). France: Sandrine Faivre (Hôpital Beaujon, Clichy), Armand Abergel (CHU de Clermont-Ferrand–Hôpital d’Estaing, Clermont Ferrand), Michel Doffoel (HUS–Nouvel Hôpital Civil, Strasbourg), Cyrille Féray (Hôtel-Dieu Hospital, Nantes), René Gerolami Santandrea (AP-HP Hôpital de la Conception, Marseille), Alexandra Heurgué-Berlot (Hôpital Robert Debré, Reims), Come Lepage (CHU–Hôpital du Bocage, Dijon), Phillipe Merle (Hôpital de la Croix Rousse, Lyon), Pierre Michel (CHU de Rouen, Rouen), Laurent Mineur (Institut Sainte Catherine, Avignon), Eric Nguyen-Khac (CHU d’Amiens–Hôpital Nord, Amiens), Isabelle Ollivier (CHU d’Amiens–Hôpital Côte de Nacre, Caen), Jean Marc Phelip (CHU de Saint Etienne–Hôpital Nord, Saint Priest en Jarez), Albert Tran (Hôpital de l’Archet 2, Nice). Germany: Christoph Antoni (University Medical Centre Mannheim, University of Heidelberg, Mannheim), Thomas Berg (Univ. Klinikum Leipzig, Leipzig), Michael Geissler (Städt Kliniken Esslingen, Esslingen), Frank Kolligs (Klinikum der Univ. München–Grosshadern, Munich), Michael Scheurlen (Klinik der Universität Würzburg, Würzburg), Eckart Schott (Charité Berlin Campus Vircho-Klinikum, Berlin), Joerg Schlaak (University Hospital Essen, Essen), Cameron Silke (Universitätskliniken Göttingen, Göttingen), Jörg Trojan (Universitätsklinikum Frankfurt, Frankfurt), Henning Wege (Universitätsklinikum Hamburg-Eppendorf, Hamburg). Greece: Christos Papandreou (University General Hospital of Larisa, Larisa), Amanda Psyrri (Attikon University General Hospital of Athens, Athens), Nikolaos Touroutoglou (Interbalkan Medical Center, Thessaloniki). Hungary: András Csejtei (Markusovszky Korhaz, Szombathely), István Láng (Orszagos Onkologiai Intezet, Budapest), János Szántó (Institute of Oncology, Medical and Health Science Center, University of Debrecen, Debrecen), László Thurzó (SZOTE Onkoterapias Klinika Szeged). Israel: Dan Aderka (Chaim Sheba Medical Center, Ramat Gan), Salomon Stemmer (Rabin Medical Center, Petah-Tiqva). Italy: Raffaele Addeo (Osp. Presidio Ospedaliero S. Giovanni di Dio, Frattamaggiore), Carlo Barone (Policlinico Univ A Gemelli–Univ Cattolica del Sacro Cuore, Rome), Antonio Bernardo (Fondzione Salvatore Maugeri IRCCS–1st Scientifico Pavia, Pavia), Luigi Bolondi (Az Osp. di Bologna Policl. S. Orsola-Malpighi, Bologna), Ignazio Carrea (Az Osp. Univ. Policlinico P. Giaccone Università Studi Palermo, Palermo), Francesco Cognetti (Istituti Fisioterapici Ospitalieri–Polo Onco. Regine Elena, Rome), Massimo Colombo (Fond. IRCCS Cà Granda Osp. Maggiore Policlinico, Milan), Camillo Porta (Fodazione IRCCS Policlinico S. Matteo, Univ. degli Studi Pavia, Pavia), Fabio Farinati (Azienda Ospedaliera–Università di Padova, Univer. Degli Studi, Padova), Sergio Frustaci (Centro di Riferimento Oncologico IRCCS, Aviano), Rosario Vincenzo Iaffaioli (IRCCS Fondazione G Pascale, Napoli), Gabriele Luppi (A.O. Univ Policl de Modena, Univ. Studi Modena e R. Emilia, Modena), Sante Romito (AO Universitaria OO.RR Foggia–Presidio Osp Riuniti Foggia, Foggia). Japan: Masayuki Furukawa (National Kyushu Cancer Center, Fukuoka), Masafumi Ikeda (National Cancer Center Hospital East, Kashiwa), Yoshitaka Inaba (Aichi Cancer Center Hospital, Aichi), Takao Iwasaki (Tohoku University Hospital, Sendai), Akihide Masumoto (Iizuka Hospital, Iizuka), Seijin Nadano (National Hospital Organization, Shikoku Cancer Center, Matsuyama), Yoichi Nishigaki (Gifu Municipal Hospital, Gifu), Kazushi Numata (Yokohama City University Medical Center, Yokohama), Takuji Okusaka (National Cancer Center Hospital Chuoku, Tokyo), Hideki Saitsu (NHO Kyushu Medical Center Fukuoka, Fukuoka), Yutaka Sasaki (Kumamoto University Hospital, Kumamoto), Takuma Teratani (Kanto Medical Center NTT EC, Shinagawa-ku), Hidenori Toyoda (Ogaki Municipal Hospital, Ogaki), Tatsuya Yamashita (Kanazawa University Hospital, Kanazawa), Osamu Yokosuka (Chiba University Hospital, Chiba). Korea: Hyun Cheol Chung (Severance Hospital, Seoul), Tae-You Kim (Seoul National University Hospital, Seoul). Spain: Jordi Bruix (Hospital Clinic I Provincial de Barcelona, Barcelona), Meritxell Casas Rodrigo (Consorci Hospitalari Parc Tauli, Barcelona), Lluis Castells Fuste (Hospital Vall D’Hebron, Barcelona), Enrique Grande Pulido (Hospital Ramon y Cajal Madrid, Madrid), Jose Montero Alvarez (Hospital Universitario Reina Sofia, Córdoba), Bruno Sangro Gomez Acebo (Clinica Universitaria de Navarra, Pamplona). Taiwan: Yee Chao (Taipei Veterans General Hospital, Taipei), Long-Bin Jeng (China Medical University Hospital, Taichung), Cheng-Yao Lin (Chi Mei Foundation Hospital–Liouying, Liouying Township), Deng-Yn Lin (Chang-Gung Memorial Hospital-Lino, Lin-Ko), Ying-Chun Shen (National Taiwan University Hospital, Taipei). Thailand: Touch Ativitavas (Ramathibodi Hospital, Bangkok), Vichien Srimuninnimit (Siriraj Hospital, Bangkok). United States: Jared Acoba (Queen’s Medical Center, Honolulu, Hawaii), Sanjiv Agarwala (St Luke’s Hospital and Health Network, Bethlehem, Pennsylvania), Ari Baron (California Pacific Medical Center, San Francisco), J. Thaddeus Beck (Highlands Oncology Group, Fayetteville, Arkansas), Allen Cohn (Rocky Mountain Cancer Centers, Denver, Colorado), David Cosgrove (Sidney Kimmel Cancer Center at Johns Hopkins Hospital, Baltimore, Maryland), Bradley Freilich (Midwest Cancer Care Physicians, Kansas City, Missouri), William Harris (Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, Washington), Aram Hezel (University of Rochester Medical Center, Rochester, New York), Haresh Jhangiani (Compassionate Cancer Care Medical Group, Fountain Valley, Fountain Valley, California), Roy MacKintosh (VA Sierra Nevada Health Care System, Reno), Anthony Reid (University of California, San Diego, La Jolla), Spencer Shao (Northwest Cancer Specialists, Portland, Oregon), Carlos Taboada (Methodist Charlton Cancer Center, Dallas, Texas), Udit Verma (University of Texas Southwestern Medical Center, Dallas).