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Proffered paper session - Gastrointestinal tumours, non colorectal

1405 - Randomized phase III study of Gemcitabine, Cisplatin plus S-1 (GCS) versus Gemcitabine, Cisplatin (GC) for Advanced Biliary Tract Cancer (KHBO1401-MITSUBA)

Date

21 Oct 2018

Session

Proffered paper session - Gastrointestinal tumours, non colorectal

Topics

Cytotoxic Therapy

Tumour Site

Hepatobiliary Cancers

Presenters

Daisuke Sakai

Citation

Annals of Oncology (2018) 29 (suppl_8): viii205-viii270. 10.1093/annonc/mdy282

Authors

D. Sakai1, M. Kanai2, S. Kobayashi3, H. Eguchi4, H. Baba5, S. Seo6, A. Taketomi7, T. Takayama8, H. Yamaue9, C. Ishioka10, M. Sho11, Y. Takeyama12, J. Fujimoto13, M. Toyoda14, J. Shimizu15, T. Goto16, K. Yoshimura17, E. Hatano13, H. Nagano18, T. Ioka19

Author affiliations

  • 1 Department Of Frontier Science For Cancer And Chemotherapy, Osaka University Graduate School of Medicine, 565-0871 - Suita/JP
  • 2 Department Of Clinical Oncology And Pharmacogenomics, Graduate School of Medicine, Kyoto University, Kyoto/JP
  • 3 Department Of Surgery, Osaka International Cancer Institute, 537-8511 - Osaka/JP
  • 4 Department Of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 565-0871 - Suita/JP
  • 5 Department Of Gastroenterological Surgery, Graduate School Of Medical Sciences, Kumamoto University, Kumamoto/JP
  • 6 Department Of Surgery, Graduate School of Medicine, Kyoto University, Kyoto/JP
  • 7 Department Of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo/JP
  • 8 Department Of Digestive Surgery, Nihon University School of Medicine, 173-8610 - Tokyo/JP
  • 9 Second Department Of Surgery, Wakayama Medical University, School of Medicine, Wakayama/JP
  • 10 Department Of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 980-8575 - Sendai/JP
  • 11 Department Of Surgery, Nara Medical University, Nara/JP
  • 12 Department Of Surgery, Kinki University Faculty of Medicine, Osaka-sayama/JP
  • 13 Department Of Surgery, Hyogo College of Medicine, Nishinomiya/JP
  • 14 Division Of Medical Oncology/hematology, Kobe University Graduate School of Medicine, 650-0017 - Kobe/JP
  • 15 Department Of Surgery, Osaka Rosai Hospital, Osaka/JP
  • 16 Division Of Gastroenterology And Hematology/oncology, Department Of Medicine, Asahikawa Medical University, Asahikawa/JP
  • 17 Innovative Clinical research Center, Kanazawa University, 920-8641 - Kanazawa/JP
  • 18 Department Of Gastroenterological, Breast And Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi/JP
  • 19 Department Of Cancer Survey And Gastrointestinal Oncology, Osaka International Cancer Institute, 537-8511 - Osaka/JP
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Abstract 1405

Background

GC has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). This phase III study aimed to confirm the superiority of GCS to GC in terms of survival in patients with unresectable or recurrent BTC.

Methods

Eligibility criteria included chemotherapy-naïve patients with advanced biliary tract adenocarcinoma (gallbladder, intrahepatic/ extrahepatic biliary tract, or ampulla of Vater), PS of 0–2, and adequate organ function. Enrolled patients were randomly allocated to either GCS arm or GC arm. In the GCS arm, gemcitabine and cisplatin were administered intravenously at doses of 1,000 or 25 mg/m2, respectively, on day 1, and oral S-1 were administered daily at a dose of 80 mg/m2 on days 1-7 every 2 weeks. In the GC arm, 1000 mg/m2 of gemcitabine and 25 mg/m2 of cisplatin were infused on days 1 and 8 and repeated every 3 weeks. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response rate (RR), and adverse events (AEs). The sample size was calculated to be 240, assumed 1 year OS rate of 43 % in GC and of 55 % in GCS (one-sided α 0.05, and power 0.8). A total of 39 institutions in Japan participated in this study.

Results

From July 2014 to February 2016, 246 patients were enrolled. At the data cutoff (April 16, 2018), median OS and 1-year OS rate was 13.5 months and 59.4 % in the GCS arm and 12.6 months and 53.7 % in the GC arm, respectively (HR 0.79, 95% confidential interval [CI] 0.60-1.04; p = 0.046 [stratified log-rank test]). Median PFS was 7.4 months in the GCS arm and 5.5 months in the GC arm (HR 0.75, 95% CI 0.58-0.97; p = 0.0015). RR was 41.5 % in the GCS arm, and 15.0 % in the GC arm. AEs except for those related to S-1 did not show significant differences between two arms.

Conclusions

This phase III study demonstrated the significant survival benefits of GCS treatment over GC treatment, and indicated that GCS could be a new standard treatment for patients with advanced BTC.

Clinical trial identification

NCT02182778, UMIN 000014371.

Legal entity responsible for the study

Kansai Hepatobiliary Oncology Group (KHBO).

Funding

Kansai Hepatobiliary Oncology Group (KHBO) Taiho Pharmaceutical Co., Ltd.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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