Landmark survival analysis and impact of anatomic site of origin in prospective clinical trials of biliary tract cancer

JOURNAL OF HEPATOLOGY

卷:73

Article

McNamara, Mairead Geraldine^1,2  Lopes, Andre^3,4  Wasan, Harpreet⁵  Malka, David⁶  Goldstein, David⁷  Shannon, Jenny⁸  Okusaka, Takuji⁹  Knox, Jennifer J.¹⁰  Wagner, Anna Dorothea¹¹  Andre, Thierry^12,13  Cunningham, David¹⁴  Moehler, Markus¹⁵  Jensen, Lars Henrik¹⁶  Koeberle, Dieter¹⁷  Bekaii-Saab, Tanios¹⁸  Bridgewater, John¹⁹  Valle, Juan W.^1,2 

[1] Univ Manchester, Div Canc Sci, Manchester M20 4BX, Lancs, England

[2] Christie NHS Fdn Trust, Manchester M20 4BX, Lancs, England

[3] Canc Res UK, London WC1E 6BT, England

[4] UCL Canc Trials Ctr, London WC1E 6BT, England

[5] Imperial Healthcare, London WI2 0NN, England

[6] Inst Gustave Roussy, Villejuif, France

[7] Univ New South Wales, Prince Wales Clin Sch, Sydney, NSW 2052, Australia

[8] Univ Sydney, Sydney, NSW 2006, Australia

[9] Natl Canc Ctr, Tokyo 1040045, Japan

[10] Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada

[11] CHU Vaudois, CH-1011 Lausanne, Switzerland

[12] Sorbonne Univ, F-75012 Paris, France

[13] Hop St Antoine, F-75012 Paris, France

[14] Royal Marsden Hosp, London, England

[15] Univ Med Mainz, D-55122 Mainz, Germany

[16] Vejle Univ Hosp, DK-7100 Vejle, Denmark

[17] St Clara Hosp, Leiter Med Klin, Chefarzt Onkol, CH-4016 Basel, Switzerland

[18] Mayo Clin, Phoenix, AZ 85054 USA

[19] UCL Canc Inst, London WC1E 6BT, England

关键词: Biliary tract cancer;    Primary site;    Overall survival;    Landmark survival;    First-line clinical trials;   

DOI  :  10.1016/j.jhep.2020.05.014

来源: Elsevier

【 摘 要 】

Background & Aims: Whether all patients with advanced biliary tract cancer (aBTC) should be included in prospective trials, irrespective of the anatomic site of origin, is debated. Herein, we aimed to assess the survival impact of anatomic site of origin in prospective clinical trials of aBTC using landmark survival analysis. Methods: Patients enrolled into prospective first-line aBTC clinical trials (Jan 97-Dec 15) were included. Overall survival (OS) was analysed using Cox proportional hazard regression; landmark survival (LS) and 95% CIs were calculated. Results: Overall, 1,333 patients were included: median age 63 years (range 23-85); 46% male; 84% ECOG-PS0/1; 25% with locally advanced disease, 72% with metastatic, 3% not reported (NR). Patients were treated with mono-chemotherapy (23%), cisplatin/gemcitabine (36%), other combinations (39%), or NR (2%). Median OS was 10.2 months (95% CI 9.6-10.9). All sites (treatment-adjusted) had decreased risk of death vs. gallbladder cancer (GBC) (p<0.001). This reduced risk vs. GBC was maintained in those receiving cisplatin/gemcitabine for extrahepatic cholangiocarcinoma (p<0.001) and intrahepatic cholangiocarcinoma (IHC, p<0.001), but not in cholangiocarcinoma-not specified (CCA-NS, p = 0.82) or ampullary carcinoma (p = 0.96). One-year OS rates amongst patients who survived beyond 1, 2, 3 and 4 years post-trial registration were 37%, 45%, 61%, and 63%, respectively. For patients who survived 1 year, those receiving combination therapy vs. mono (p = 0.008) (acknowledging potential selection bias) and those with IHC and CCA-NS vs. GBC had better LS (both p<0.05). Metastatic disease was associated with shorter LS than locally advanced disease (p = 0.002). ECOG-PS and gender were not associated with LS (p>0.05, p = 0.08 respectively). Conclusions: GBC is associated with worse OS than other BTC sites and should be considered as a stratification factor in clinical trials. LS rates enable adjusted prognostication for aBTC survivors. Lay summary: Patients with gallbladder cancer have worse overall survival compared to those with biliary tract cancers of different primary origin. Thus, gallbladder cancer should be considered as a stratification factor in future clinical trials. Landmark survival rates enable adjusted prognosis prediction for patients with advanced biliary tract cancer who survive for some time. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

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