The SACURA trial is a phase III study to evaluate the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone in stage II colon cancer, in which survival benefit of 1-year UFT was not demonstrated (Eur J Cancer 96:54-63, 2018). In an additional biomarker study, we studied MSI status and 18qLOH of cancer tissues and evaluated their clinical value in stage II colon cancer patients.
A total of 1026 samples were collected from patients enrolled in the SACURA trial. MSI was evaluated by 5 markers; BAT25, BAT26, D2S123, D5S346, and D17S250. MSI-high (MSI-H) was defined as the presence of instability in more than 20% of the markers. 18qLOH was evaluated by 3 markers; D18S69, D18S74E, and D18S851. 18qLOH positivity was defined as the presence of LOH in any of the 18q markers. 18q LOH negativity was strictly defined as the presence of at least one informative markers and the absence of LOH.
MSI-H was observed in 74 (7.2%) patients. The 18q LOH was present in 526 patients (51.3%) and LOH negativity was observed in 354 (34.5%). Informative LOH data was not available in 146 patients (14.2%). Relapse free survival (RFS) in MSI-H patients was better than that in non MSI-H (HR: 0.40, 95%CI: 0.17-0.98, p = 0.045). RFS in 18qLOH positive patients was significantly worse than in 18qLOH negative patients (hazard ratio: 1.44, 95%CI: 1.01-2.07, p = 0.047). When the patients were divided into 3 groups using MSI status and 18qLOH, approximately 5% differences of RFS were observed among the subgroups (Table). In the group 1 and 2, 5-year RFS rates were favorable and there were no differences in RFS between the treatment arms. In the group 3, 5-year RFS rate in the UFT group was +3% better than in the surgery-alone group although the difference was not significant.Table: 520P
|5yRFS in the subgroups divided by MSI status and 18qLOH|
|Subgroup divided by MSI status and 18qLOH||5yRFS|
|Overall||Surgery- alone group||UFT group|
|group 1: MSI-H||92.9% (N = 74)||94.3% (N = 36)||91.7% (N = 38)|
|group 2: non MSI-H and 18qLOH negative||87.2% (N = 327)||87.5% (N = 153)||87.0% (N = 174)|
|group 3: non MSI-H and 18qLOH positive/non- informative||82.5% (N = 625)||81.0% (N = 320)||84.0% (N = 305)|
In stage II colon cancer, adjuvant chemotherapy might be unnecessary for MSI-H or 18qLOH negative patients. MSI status and 18qLOH might be useful biomarkers in stage II colon cancers.
Clinical trial identification
Legal entity responsible for the study
Sacura Study Group.
The Foundation for Biomedical Research and Innovation, Translational Research Informatics Center (TRI), under the funding contract with Taiho Pharmaceutical Co. Ltd.
This study was supported by the Foundation for Biomedical Research and Innovation, Translational Research Informatics Center (TRI), under the funding contract with Taiho Pharmaceutical Co. Ltd., Japan.
We are grateful to all the patients and the co-investigators for their cooperation in the SACURA trial.
The authors also thank the following collaborators for their contributions to this trial: Kenichi KONO, Satoshi NAKAGAWA, Yasuyo KUSUNOKI, Fumie KINOSHITA, and Naoko KASHIWAGI in data management, Tasuku INAJI, Hayami TSUMURA, Akinori OGASAWARA, Yuri UEDA and Syuichiro SUGIMOTO as the project office staff, Satomi SAKABAYASHI, Yoshihiro MATSUBARA and Tatsuo KAGIMURA as the statistical staff, and Prof. Masanori FUKUSHIMA as a director of the Translational Research Informatics Center.
T. Ishikawa: Honoraria: Chugai Pharma, Merck Serono, Takeda, Sanofi, Taiho Pharmaceutical; Research funding: Taiho Pharmaceutical. M. Ishiguro: Honoraria: Chugai Pharma, Merck Serono, Takeda, Sanofi, Taiho Pharmaceutical; Advisory role: Taiho Pharmaceutical; Research funding: Yakult, Taiho Pharmaceutical. H. Ueno: Honoraria: Chugai Pharma, Yakult, Eazai, Taiho Pharmaceutical. H. Uetake: Honoraria: Chugai Pharma, Merck Serono, Takeda, Taiho Pharmaceutical; Advisory role: Sanofi; Research funding: Taiho Pharmaceutical. N. Tomita: Research funding: Chugai Pharma, Taiho Pharmaceutical. Y. Shimada: Honoraria: Chugai Pharma, Yakult, Takeda, Lilly, Taiho Pharmaceutical; Research funding Merk Serono, Lilly, MSD, Taiho Pharmaceutical. K. Kotake: Honoraria: Chugai Pharma, Bristol-Myers Squibb, Taiho Pharmaceutical. M. Watanabe: Honoraria: Taiho Pharmaceutical: Research funding: Taiho Pharmaceutical: Travel and accommodations: Taiho Pharmaceutical. H. Mochizuki: Honoraria: Becton, Dickinson and Company, Taiho Pharmaceutical; Advisory role: Otsuka Pharmaceutical. K. Sugihara: Honoraria: Chugai Pharma, Lilly, Novertis, Bayer, Taiho Pharmaceutical; Advisory role: Otsuka Pharmaceutical; Research funding: Chugai Pharma, Takeda, Taiho Pharmaceutical. All other authors have declared no conflicts of interest.