Individual-patient-based data meta-analysis of randomized trials in gastric cancer

• Project/Area Number: 15H05661
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Epidemiology and preventive medicine
• Research Institution: The University of Tokyo
• Principal Investigator: OBA Koji 東京大学, 大学院情報学環・学際情報学府, 准教授 (30422926)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: メタアナリシス / 代替エンドポイント / 臨床疫学 / 胃癌 / データシェアリング / 国際共同研究 / 生物統計学 / 臨床試験 / 悪性腫瘍

Outline of Final Research Achievements

We could collect individual-patient-data (IPD) of 6,843 individuals from 17 previous randomized controlled trials conducted around the world in advanced or recurrent gastric cancer.Together with the GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research through International Collaboration）1st round data, the total number of patients reached to 10,912 individuals of randomized controlled trials in advanced or recurrent gastric cancer. Using these data, it was shown that the progression-free survival (PFS) could be a surrogate endpoint for overall survival (OS), the gold standard endpoint for evaluating treatment for advanced or recurrent gastric cancer. Meaningful results were obtained for better and earlier drug development in future.

Academic Significance and Societal Importance of the Research Achievements

進行・再発胃がんにおいて、標準治療として確立されるためには全生存期間でその有効性を示す必要がある。近年、治療成績の向上だけでなく2次治療以降の治療が充実してきていることから差が検出し難くなっており、より多くの患者数やより長期の追跡期間が必要となっている。本研究では、全生存期間の代わりに無増悪生存期間を代替エンドポイントとすることで早期に妥当な評価を行えることを示すことができた。近年、新規治療法にかかる開発コストが非常に高価になってきていることからも、その意義は大きい。また、国際的な協力のもと、胃癌領域で世界最大規模の個人データに基づく臨床試験データベースを構築することができた。

Research Products

• [Int'l Joint Research] Institut Gustav Roussy/Institut Curie/CHU Robert Debre(フランス)
• [Int'l Joint Research] Hasselt University/KU Leuven(ベルギー)
• [Int'l Joint Research] Seoul National University(韓国)
• [Int'l Joint Research] Johannes Gutenberg-University Clinic(ドイツ)
• [Int'l Joint Research] Institute Gustav Roussy(フランス)
• [Int'l Joint Research] Institut Gustave Roussy/Hospitalier Universitaire Robert Debre(France)
• [Int'l Joint Research] Hasselt University/IDDI/University Hospital Gasthuisberg(Belgium)
• [Int'l Joint Research] Seoul University(韓国)
• [Int'l Joint Research] Institut Gustav Roussy(フランス)
• [Journal Article] Efficacy and Safety of Polaprezinc (Zinc Compound) on Zinc Deficiency: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials Using Individual Patient Data. (2020)
  • Author(s): Furihata K, Tsuchikawa M, Miwa T, Naito Y, Oba K, Sakagami M.
  • Journal Title: Nutrients Volume: 12 Issue: 4 Pages: 1128-1128
  • DOI: 10.3390/nu12041128
  • Peer Reviewed
• [Journal Article] Relationship Between the Waiting Times for Surgery and Survival in Patients with Gastric Cancer. (2020)
  • Author(s): Kumazu Y, Oba K, Hayashi T, Yamada T, Hara K, Osakabe H, Shimoda Y, Nakazono M, Nagasawa S, Rino Y, Masuda M, Ogata T, Yoshikawa T, Oshima T.
  • Journal Title: World J Surg Volume: 44 Issue: 4 Pages: 1209-1215
  • DOI: 10.1007/s00268-020-05367-8
  • Peer Reviewed
• [Journal Article] Lymph node retrieval after colorectal cancer surgery: a comparative study of the efficacy between the conventional manual method and a new fat dissolution method. (2020)
  • Author(s): Fujieda Y, Maeda H, Oba K, Okamoto K, Fukudome I, Shiga M, Kawanishi Y, Akimori T, Kuroiwa H, Nishimoto H, Namikawa T, Murakami I, Kobayashi M, Hanazaki K.
  • Journal Title: Surg Today Volume: - Issue: 7 Pages: 726-733
  • DOI: 10.1007/s00595-019-01944-0
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive Comparative Analysis of Prognostic Value of Systemic Inflammatory Biomarkers for Patients with Stage II/III Colon Cancer (2019)
  • Author(s): Suzuki S, Akiyoshi T, Oba K, Otsuka F, Tominaga T, Nagasaki T, Fukunaga Y, Ueno M
  • Journal Title: Ann Surg Oncol Volume: 27 Issue: 3 Pages: 844-852
  • DOI: 10.1245/s10434-019-07904-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association between polymorphisms in EGFR and tumor response during cetuximab and oxaliplatin-based combination therapy in metastatic colorectal cancer: Analysis of data from two clinical trials (2019)
  • Author(s): Maeda H, Hazama S, Iwamoto S, Oba K, Tsunedomi R, Okayama N, Suehiro Y, Yamasaki T, Nakagami Y, Suzuki N, Nagano H, Sakamoto J, Mishima H, Nagata N
  • Journal Title: Oncol Lett Volume: 18(5) Pages: 4555-4562
  • DOI: 10.3892/ol.2019.10787
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] JOIN trial: treatment outcome and recovery status of peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer. (2019)
  • Author(s): Yoshino T, Kotaka M, Shinozaki K, Touyama T, Manaka D, Matsui T, Ishigure K, Hasegawa J, Inoue K, Munemoto Y, Takagane A, Ishikawa H, Ishida H, Ogata Y, Oba K, Goto K, Sakamoto J, Maehara Y, Ohtsu A.
  • Journal Title: Cancer Chemother Pharmacol Volume: 84(6) Issue: 6 Pages: 1269-1277
  • DOI: 10.1007/s00280-019-03957-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] SAPPHIRE: a randomised phase II study of planned discontinuation or continuous treatment of oxaliplatin after six cycles of modified FOLFOX6 plus panitumumab in patients with colorectal cancer. (2019)
  • Author(s): Munemoto Y, Nakamura M, Takahashi M, Kotaka M, Kuroda H, Kato T, Minagawa N, Noura S, Fukunaga M, Kuramochi H, Touyama T, Takahashi T, Miwa K, Satake H, Kurosawa S, Miura T, Mishima H, Sakamoto J, Oba K, Nagata N.
  • Journal Title: Eur J Cancer Volume: 119 Pages: 158-167
  • DOI: 10.1016/j.ejca.2019.07.006
  • Peer Reviewed
• [Journal Article] Prognostic impact of residual lateral lymph node metastasis after neoadjuvant (chemo)radiotherapy in patients with advanced low rectal cancer (2019)
  • Author(s): Akiyoshi T, Toda S, Tominaga T, Oba K, Tomizawa K, Hanaoka Y, Nagasaki T, Konishi T, Matoba S, Fukunaga Y, Ueno M, Kuroyanagi H
  • Journal Title: BJS Open Volume: 3 Issue: 6 Pages: 822-829
  • DOI: 10.1002/bjs5.50194
  • Peer Reviewed / Open Access
• [Journal Article] Detection of atypical data in multicenter clinical trials using unsupervised statistical monitoring (2019)
  • Author(s): Trotta Laura、Kabeya Yuusuke、Buyse Marc、Doffagne Erik、Venet David、Desmet Lieven、Burzykowski Tomasz、Tsuburaya Akira、Yoshida Kazuhiro、Miyashita Yumi、Morita Satoshi、Sakamoto Junichi、Praveen Paurush、Oba Koji
  • Journal Title: Clinical Trials Volume: 16 Issue: 5 Pages: 512-522
  • DOI: 10.1177/1740774519862564
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development and Validation of a Prediction Model for Organ-Specific Recurrences After Curative Resection of Colon Cancer (2019)
  • Author(s): Nagata Hiroshi、Ishihara Soichiro、Oba Koji、Tanaka Toshiaki、Hata Keisuke、Kawai Kazushige、Nozawa Hiroaki
  • Journal Title: Diseases of the Colon & Rectum Volume: 62 Issue: 9 Pages: 1043-1054
  • DOI: 10.1097/dcr.0000000000001430
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] One‐Day Versus Three‐Day Dexamethasone in Combination with Palonosetron for the Prevention of Chemotherapy‐Induced Nausea and Vomiting: A Systematic Review and Individual Patient Data‐Based Meta‐Analysis (2019)
  • Author(s): Okada Yuki、Oba Koji、Furukawa Naoto、Kosaka Yoshimasa、Okita Kenji、Yuki Satoshi、Komatsu Yoshito、Celio Luigi、Aapro Matti
  • Journal Title: The Oncologist Volume: 24 Issue: 12 Pages: 1593-1600
  • DOI: 10.1634/theoncologist.2019-0133
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer (2019)
  • Author(s): Akiyoshi T, Tanaka N, Kiyotani K, Gotoh O, Yamamoto N, Oba K, Fukunaga Y, Ueno M, Mori S
  • Journal Title: Br J Surg Volume: 106 Issue: 10 Pages: 1381-1392
  • DOI: 10.1002/bjs.11179
  • Peer Reviewed
• [Journal Article] Biweekly S-1 plus oxaliplatin (SOX) reintroduction in previously treated metastatic colorectal cancer patients (ORION 2 study): a phase II study to evaluate the efficacy and safety (2019)
  • Author(s): Tanioka H, Honda M, Tanaka C, Morita Y, Ishibashi K, Kato T, Matsuda C, Kataoka M, Satake H, Munemoto Y, Kobayashi K, Takahashi M, Nakata K, Sakamoto J, Oba K, Mishima H
  • Journal Title: Int J Clin Oncol Volume: 24 Issue: 7 Pages: 836-841
  • DOI: 10.1007/s10147-019-01414-0
  • Peer Reviewed
• [Journal Article] A multicenter single-arm Phase II clinical trial of second-line FOLFIRI plus panitumumab after first-line treatment with FOLFOX plus panitumumab for initial RAS wild-type colorectal cancer with evaluation of circulating tumor DNA: A protocol study (2019)
  • Author(s): Maeda H, Nagata N, Nagasaka T, Oba K, Mishima H, Kato T, Yoshida K, Muro K, Sakamoto J
  • Journal Title: Oncol Lett Volume: 17 Pages: 1980-1985
  • DOI: 10.3892/ol.2018.9763
  • Peer Reviewed
• [Journal Article] Efficacy of CapeOX plus Cetuximab Treatment as a First-Line Therapy for Patients with Extended RAS/BRAF/PIK3CA Wild-Type Advanced or Metastatic Colorectal Cancer. (2018)
  • Author(s): Iwamoto S, Maeda H, Hazama S, Oba K, Okayama N, Suehiro Y, Yamasaki T, Suzuki N, Nagano H, Sakamoto J, Mishima H, Nagata N
  • Journal Title: Journal of Cancer Volume: 9(22) Issue: 22 Pages: 4092-4098
  • DOI: 10.7150/jca.26840
  • Peer Reviewed / Open Access
• [Journal Article] A randomized phase III study of hepatic arterial infusion chemotherapy with 5-fluorouracil and subsequent systemic chemotherapy versus systemic chemotherapy alone for colorectal cancer patients with curatively resected liver metastases (Japanese Foundation for Multidisciplinary Treatment of Cancer 32) (2018)
  • Author(s): Kusano M, Aoyama T, Okabayashi K, Hirata K, Tsuji Y, Nakamori S, Asahara T, Ohashi Y, Yoshikawa T, Sakamoto J, Oba K, Saji S
  • Journal Title: J Cancer Res Ther Volume: 14 Issue: 10 Pages: 761-761
  • DOI: 10.4103/0973-1482.179188
  • Peer Reviewed
• [Journal Article] A phase II study of bevacizumab and irinotecan plus alternate-day S-1 as a second-line therapy in patients with metastatic colorectal cancer: the AIRS study. (2018)
  • Author(s): Matsuda C, Honda M, Tanaka C, Kondo K, Takahashi T, Kosugi C, Tokunaga Y, Takemoto H, Kim HM, Sakamoto J, Oba K, Mishima H
  • Journal Title: Cancer Chemother Pharmacol Volume: 81 Issue: 6 Pages: 1035-1041
  • DOI: 10.1007/s00280-018-3568-x
  • Peer Reviewed
• [Journal Article] Development and Validation of a Prediction Model for Postoperative Peritoneal Metastasis After Curative Resection of Colon Cancer. (2018)
  • Author(s): Nagata H, Ishihara S, Oba K, Tanaka T, Hata K, Kawai K, Nozawa H.
  • Journal Title: Ann Surg Oncol Volume: 25 Issue: 5 Pages: 1366-1373
  • DOI: 10.1245/s10434-018-6403-z
  • Peer Reviewed
• [Journal Article] A phase II trial to evaluate the efficacy of panitumumab combined with fluorouracil-based chemotherapy for metastatic colorectal cancer: the PF trial. (2018)
  • Author(s): Munemoto Y, Kanda M, Oba K, Kim HM, Takemoto H, Denda T, Nagata N, Takano N, Fukunaga M, Kataoka M, Tokunaga Y, Sakamoto J, Mishima H.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 81 Issue: 5 Pages: 829-838
  • DOI: 10.1007/s00280-018-3556-1
  • Peer Reviewed
• [Journal Article] Treatment using oxaliplatin and S-1 adjuvant chemotherapy for pathological stage III gastric cancer: a multicenter phase II study (TOSA trial) protocol. (2018)
  • Author(s): Namikawa T, Maeda H, Kitagawa H, Oba K, Tsuji A, Yoshikawa T, Kobayashi M, Hanazaki K.
  • Journal Title: BMC Cancer. Volume: 18 Issue: 1 Pages: 186-186
  • DOI: 10.1186/s12885-018-4109-z
  • Peer Reviewed / Open Access
• [Journal Article] Lymph node retrieval after dissolution of surrounding adipose tissue for pathological examination of colorectal cancer. (2018)
  • Author(s): Maeda H, Okamoto K, Oba K, Shiga M, Fujieda Y, Namikawa T, Hiroi M, Murakami I, Hanazaki K, Kobayashi M.
  • Journal Title: Oncol Lett. Volume: 15 Pages: 2495-2500
  • DOI: 10.3892/ol.2017.7629
  • Peer Reviewed
• [Journal Article] Meta-analysis of randomized clinical trials in the era of individual patient data sharing. (2018)
  • Author(s): Kawahara T, Fukuda M, Oba K, Sakamoto J, Buyse M.
  • Journal Title: Int J Clin Oncol Volume: 23 Issue: 3 Pages: 403-409
  • DOI: 10.1007/s10147-018-1237-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer (2018)
  • Author(s): Ogura Atsushi、Akiyoshi Takashi、Yamamoto Noriko、Kawachi Hiroshi、Ishikawa Yuichi、Mori Seiichi、Oba Koji、Nagino Masato、Fukunaga Yosuke、Ueno Masashi
  • Journal Title: European Journal of Cancer Volume: 91 Pages: 11-20
  • DOI: 10.1016/j.ejca.2017.12.005
  • Peer Reviewed / Open Access
• [Journal Article] Risk factors for peritoneal recurrence in stage II-III colon cancer (2018)
  • Author(s): Mayanagi S, Kashiwabara K, Honda M, Oba K, Aoyama T, Kanda M, Maeda H, Hamada C, Sadahiro S, Sakamoto J, Saji S, Yoshikawa T
  • Journal Title: Dis Colon Rectum Volume: 61 Issue: 7 Pages: 803-808
  • DOI: 10.1097/dcr.0000000000001002
  • Peer Reviewed
• [Journal Article] Clinical Signatures of Mucinous and Poorly Differentiated Subtypes of Colorectal Adenocarcinomas by a Propensity Score Analysis of an Independent Patient Database from Three Phase III Trials. (2018)
  • Author(s): Kanda M, Oba K, Aoyama T, Kashiwabara K, Mayanagi S, Maeda H, Honda M, Hamada C, Sadahiro S, Sakamoto J, Saji S, Yoshikawa T.
  • Journal Title: Dis Colon Rectum Volume: 61 Issue: 4 Pages: 461-471
  • DOI: 10.1097/dcr.0000000000001022
  • Peer Reviewed
• [Journal Article] ネットワークメタアナリシス：Stent thrombosis with drug-eluting and bare-metal stents: Evidence from a comprehensive network meta-analysis. (2017)
  • Author(s): 大庭幸治
  • Journal Title: Coronary intervention Volume: 13 Pages: 56-62
• [Journal Article] Statistical evaluation of surrogate endpoints with examples from cancer clinical trials. (2016)
  • Author(s): Buyse M, Molenberghs G, Paoletti X, Oba K, Alonso A, Van der Elst W, Burzykowski T.
  • Journal Title: Biom J Volume: 58 Issue: 1 Pages: 104-132
  • DOI: 10.1002/bimj.201400049
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in advanced/recurrent gastric cancer (AGC) treatment: Individual-patient-data (IPD) based meta-analysis of randomized trials. (2020)
  • Author(s): Oba K, Paoletti X, Bang YJ, Michiels S, Moehler M, Morita S, Ohashi Y, Bouche; O, Sakamoto J, Sasako M, Shitara K, VanCutsem E, Buyse M, Burzykowski T, and the GASTRIC
  • Organizer: 2020 ASCO Annual Meeting
  • Int'l Joint Research
• [Book] Sample Size Calculations for Phase III Trials in Oncology. In: Halabi S, Michiels S (Eds.) Textbook of Clinical Trials in Oncology: A Statistical Perspective (2019)
  • Author(s): Oba K, Kuchiba A
  • Total Pages: 626
  • Publisher: CRC Press
  • ISBN: 9781138083776
• [Book] Statistical evaluation of surrogate endpoints in cancer clinical trials. (In: Oncology Clinical Trials: Successful Design, Conduct and Analysis.) (2018)
  • Author(s): Marc Buyse, Geert Molenberghs, Xavier Paoletti, Koji Oba, Ariel Alonso, Wim Van der Elst, and Tomasz Burzykowski
  • Total Pages: 527
  • Publisher: Demos Medical Publishing
  • ISBN: 9780826168726
• [Book] Evaluation of Surrogate Endpoints Using a Meta-Analysis Approach with Individual Patient Data: Summary of a Gastric Cancer Meta-Analysis Project (in Frontiers of Biostatistical Methods and Applications in Clinical Oncology) (2017)
  • Author(s): Koji OBA, Xavier Paoletti (Shigeyuki Matsui, John Crowley Eds.)
  • Total Pages: 438
  • Publisher: Springer Singapore
  • ISBN: 9789811001246
• [Remarks] The GASTRIC
  • URL: https://gastricproject.org/
• [Remarks] GASTRIC研究の紹介ページ
  • URL: https://gastricproject.org/
• [Funded Workshop] GASTRIC investigators’ meeting in ASCO-GI 2017 (2017)