PMID- 20728210 OWN - NLM STAT- MEDLINE DCOM- 20100929 LR - 20240103 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 376 IP - 9742 DP - 2010 Aug 28 TI - Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. PG - 687-97 LID - 10.1016/S0140-6736(10)61121-X [doi] AB - BACKGROUND: Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2; also known as ERBB2), was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer. METHODS: ToGA (Trastuzumab for Gastric Cancer) was an open-label, international, phase 3, randomised controlled trial undertaken in 122 centres in 24 countries. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation. Participants were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab. Allocation was by block randomisation stratified by Eastern Cooperative Oncology Group performance status, chemotherapy regimen, extent of disease, primary cancer site, and measurability of disease, implemented with a central interactive voice recognition system. The primary endpoint was overall survival in all randomised patients who received study medication at least once. This trial is registered with ClinicalTrials.gov, number NCT01041404. FINDINGS: 594 patients were randomly assigned to study treatment (trastuzumab plus chemotherapy, n=298; chemotherapy alone, n=296), of whom 584 were included in the primary analysis (n=294; n=290). Median follow-up was 18.6 months (IQR 11-25) in the trastuzumab plus chemotherapy group and 17.1 months (9-25) in the chemotherapy alone group. Median overall survival was 13.8 months (95% CI 12-16) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months (10-13) in those assigned to chemotherapy alone (hazard ratio 0.74; 95% CI 0.60-0.91; p=0.0046). The most common adverse events in both groups were nausea (trastuzumab plus chemotherapy, 197 [67%] vs chemotherapy alone, 184 [63%]), vomiting (147 [50%] vs 134 [46%]), and neutropenia (157 [53%] vs 165 [57%]). Rates of overall grade 3 or 4 adverse events (201 [68%] vs 198 [68%]) and cardiac adverse events (17 [6%] vs 18 [6%]) did not differ between groups. INTERPRETATION: Trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer. FUNDING: F Hoffmann-La Roche. CI - Copyright 2010 Elsevier Ltd. All rights reserved. FAU - Bang, Yung-Jue AU - Bang YJ AD - Seoul National University College of Medicine, Seoul, South Korea. bangyj@snu.ac.kr FAU - Van Cutsem, Eric AU - Van Cutsem E FAU - Feyereislova, Andrea AU - Feyereislova A FAU - Chung, Hyun C AU - Chung HC FAU - Shen, Lin AU - Shen L FAU - Sawaki, Akira AU - Sawaki A FAU - Lordick, Florian AU - Lordick F FAU - Ohtsu, Atsushi AU - Ohtsu A FAU - Omuro, Yasushi AU - Omuro Y FAU - Satoh, Taroh AU - Satoh T FAU - Aprile, Giuseppe AU - Aprile G FAU - Kulikov, Evgeny AU - Kulikov E FAU - Hill, Julie AU - Hill J FAU - Lehle, Michaela AU - Lehle M FAU - Ruschoff, Josef AU - Ruschoff J FAU - Kang, Yoon-Koo AU - Kang YK CN - ToGA Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT01041404 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20100819 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0W860991D6 (Deoxycytidine) RN - 6804DJ8Z9U (Capecitabine) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - P188ANX8CK (Trastuzumab) RN - Q20Q21Q62J (Cisplatin) RN - U3P01618RT (Fluorouracil) SB - IM EIN - Lancet. 2010 Oct 16;376(9749):1302 CIN - Lancet. 2010 Aug 28;376(9742):659-60. PMID: 20728211 CIN - Nat Rev Clin Oncol. 2010 Nov;7(11):611. PMID: 21049571 CIN - Gastroenterology. 2011 Jan;140(1):356-8; discussion 358. PMID: 21087674 CIN - Lancet. 2010 Nov 20;376(9754):1735; author reply 1735-6. PMID: 21093641 CIN - Biomark Med. 2010 Dec;4(6):793. PMID: 21174864 MH - Adenocarcinoma/*drug therapy/metabolism/mortality MH - Aged MH - Antibodies, Monoclonal/*administration & dosage MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Agents/*administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage MH - Capecitabine MH - Cisplatin/administration & dosage MH - Deoxycytidine/administration & dosage/analogs & derivatives MH - Drug Therapy, Combination MH - *Esophagogastric Junction MH - Female MH - Fluorouracil/administration & dosage/analogs & derivatives MH - Humans MH - Male MH - Middle Aged MH - Receptor, ErbB-2/biosynthesis MH - Stomach Neoplasms/*drug therapy/metabolism/mortality MH - Survival Analysis MH - Trastuzumab MH - Treatment Outcome FIR - Parnis, F IR - Parnis F FIR - McKendrick, J IR - McKendrick J FIR - Price, T IR - Price T FIR - Mainwaring, P IR - Mainwaring P FIR - Van Cutsem, E IR - Van Cutsem E FIR - Forones, N IR - Forones N FIR - Olivatto, L IR - Olivatto L FIR - Miziara, J E IR - Miziara JE FIR - Li, J IR - Li J FIR - Wang, J IR - Wang J FIR - Wang, Y IR - Wang Y FIR - Zheng, L IR - Zheng L FIR - Wang, L IR - Wang L FIR - Feng-Yi, F IR - Feng-Yi F FIR - Shen, L IR - Shen L FIR - Xu, J M IR - Xu JM FIR - Jiao, S IR - Jiao S FIR - Guan, Z IR - Guan Z FIR - Yu, S-Y IR - Yu SY FIR - Pan, L IR - Pan L FIR - Jin, Y IR - Jin Y FIR - Tao, M IR - Tao M FIR - Qin, S IR - Qin S FIR - Reyes, D Otero IR - Reyes DO FIR - Valladares, R IR - Valladares R FIR - Landaverde, D IR - Landaverde D FIR - Pfeiffer, P IR - Pfeiffer P FIR - Vestlev, P M IR - Vestlev PM FIR - Tanner, M IR - Tanner M FIR - Bouche, O IR - Bouche O FIR - Michel, P IR - Michel P FIR - Jacob, J IR - Jacob J FIR - Husseini, F IR - Husseini F FIR - Metges, J-P IR - Metges JP FIR - Dominguez, S IR - Dominguez S FIR - Viret, F IR - Viret F FIR - Clemens, M IR - Clemens M FIR - zum Buschenfelde, C O Meyer IR - zum Buschenfelde CO FIR - Moehler, M IR - Moehler M FIR - Hoefeler, H IR - Hoefeler H FIR - Lordick, F IR - Lordick F FIR - Toache, L M Zetina IR - Toache LM FIR - Castro-Salguero, H IR - Castro-Salguero H FIR - Prasad, S V S S IR - Prasad SV FIR - Gangadharan, V P IR - Gangadharan VP FIR - Advani, S IR - Advani S FIR - Julka, P K IR - Julka PK FIR - Aprile, G IR - Aprile G FIR - Barone, C IR - Barone C FIR - Cascinu, S IR - Cascinu S FIR - Di Costanzo, F IR - Di Costanzo F FIR - Stefania, S IR - Stefania S FIR - Hamamoto, Y IR - Hamamoto Y FIR - Sasaki, Y IR - Sasaki Y FIR - Yamaguchi, K IR - Yamaguchi K FIR - Ohtsu, A IR - Ohtsu A FIR - Hatake, K IR - Hatake K FIR - Satoh, A IR - Satoh A FIR - Boku, N IR - Boku N FIR - Sawaki, A IR - Sawaki A FIR - Takiuchi, H IR - Takiuchi H FIR - Tamura, T IR - Tamura T FIR - Baba, E IR - Baba E FIR - Nishina, T IR - Nishina T FIR - Miyata, Y IR - Miyata Y FIR - Satoh, T IR - Satoh T FIR - Omuro, Y IR - Omuro Y FIR - Saito, H IR - Saito H FIR - Bang, Y-J IR - Bang YJ FIR - Kang, Y-K IR - Kang YK FIR - Hong, D S IR - Hong DS FIR - Jeung, H-C IR - Jeung HC FIR - Lim, H-Y IR - Lim HY FIR - Chung, H C IR - Chung HC FIR - Kim, J G IR - Kim JG FIR - Kim, Y H IR - Kim YH FIR - Lee, K IR - Lee K FIR - Park, S IR - Park S FIR - Leon, E IR - Leon E FIR - Trevino, S A IR - Trevino SA FIR - Sahui, T Suarez IR - Sahui TS FIR - Rodriguez, A L IR - Rodriguez AL FIR - Sanchez, R I Lopez IR - Sanchez RI FIR - Alvarez-Barreda, R IR - Alvarez-Barreda R FIR - de Mendoza, F Hurtado IR - de Mendoza FH FIR - Leon-Chong, J IR - Leon-Chong J FIR - Philco, M IR - Philco M FIR - Sanches, E IR - Sanches E FIR - Quintela, A IR - Quintela A FIR - Sa, A IR - Sa A FIR - Damasceno, M IR - Damasceno M FIR - Coutinho, C IR - Coutinho C FIR - Pinto, A Moreira IR - Pinto AM FIR - Teixeira, M M IR - Teixeira MM FIR - Braga, S IR - Braga S FIR - Topuzov, E IR - Topuzov E FIR - Cheporov, S IR - Cheporov S FIR - Garin, A IR - Garin A FIR - Gorbunova, V IR - Gorbunova V FIR - Lichinitser, M IR - Lichinitser M FIR - Khasanov, R S IR - Khasanov RS FIR - Manikhas, G M IR - Manikhas GM FIR - Biakhov, M IR - Biakhov M FIR - Moiseenko, V IR - Moiseenko V FIR - Gotovkin, E IR - Gotovkin E FIR - Kulikov, E IR - Kulikov E FIR - Lipatov, O IR - Lipatov O FIR - Gladkov, O IR - Gladkov O FIR - Landers, G IR - Landers G FIR - Robertson, B IR - Robertson B FIR - Gravalos, C IR - Gravalos C FIR - Queralt, B IR - Queralt B FIR - Galan, M C IR - Galan MC FIR - Gallego, R IR - Gallego R FIR - Aguilera, M J Safont IR - Aguilera MJ FIR - Martin, M IR - Martin M FIR - Fernandez-Martos, C IR - Fernandez-Martos C FIR - Chao, Y IR - Chao Y FIR - Chang, C IR - Chang C FIR - Yalcin, S IR - Yalcin S FIR - Yilmaz, U IR - Yilmaz U FIR - Evans, J IR - Evans J FIR - Falk, S IR - Falk S FIR - Mansoor, W IR - Mansoor W FIR - Ferry, D IR - Ferry D FIR - Thompson, J IR - Thompson J FIR - Gollins, S IR - Gollins S EDAT- 2010/08/24 06:00 MHDA- 2010/09/30 06:00 CRDT- 2010/08/24 06:00 PHST- 2010/08/24 06:00 [entrez] PHST- 2010/08/24 06:00 [pubmed] PHST- 2010/09/30 06:00 [medline] AID - S0140-6736(10)61121-X [pii] AID - 10.1016/S0140-6736(10)61121-X [doi] PST - ppublish SO - Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19.