TY - JOUR
T1 - Landmark survival analysis and impact of anatomic site of origin in prospective clinical trials of biliary tract cancer
AU - McNamara, Mairéad Geraldine
AU - Lopes, Andre
AU - Wasan, Harpreet
AU - Malka, David
AU - Goldstein, David
AU - Shannon, Jenny
AU - Okusaka, Takuji
AU - Knox, Jennifer J.
AU - Wagner, Anna Dorothea
AU - André, Thierry
AU - Cunningham, David
AU - Moehler, Markus
AU - Jensen, Lars Henrik
AU - Koeberle, Dieter
AU - Bekaii-Saab, Tanios
AU - Bridgewater, John
AU - Valle, Juan W.
N1 - Funding Information:
ABC-02 was an investigator-initiated study sponsored by UCL , funded by CRUK (funding reference number C1813/A4853 ) with gemcitabine provided by Lilly Oncology (unrestricted grant). Cancer Research UK was not involved in the design of the current study. They did fund the data collection for ABC-02 and analysis was performed by Andre Lopes, who is funded by CRUK . They did not have a role in the interpretation of the data or in writing the manuscript. BT22 was an Eli Lilly Japan -sponsored trial; Eli Lilly were not involved in the design of the current study. They did fund the data collection for BT22. They did not have a role in the analysis, interpretation of the data or in writing the manuscript. The ABC and TACTIC trials were Australasian Gastro Intestinal Trials Group trials funded in part by grants from Eli Lilly and Amgen , respectively, and the AGITG; additional data collection for PFS and OS was investigator-initiated and supported by the Ministry of Health, Labour, and Welfare, Health Labour Sciences Research Grant (with data transfer to CRUK & UCL CTC under a study-specific agreement). The funders were not involved in the design of the current study. They did fund the data collection for the ABC, TACTIC and AGITG studies. They did not have a role in the analysis, interpretation of the data or in writing the manuscript. JB is partly supported by the UCLH/UCL Biomedical Research Centre . The funders were not involved in the design of the current study. They did fund JB whose author contribution is described below. They did not have a role in the analysis, interpretation of the data or in writing the manuscript. AL is supported by a CRUK grant C444/A15953 to the CRUK & UCL CTC. Cancer Research UK were not involved in the design of the current study. They did fund the data collection for ABC-02 and analysis was performed by Andre Lopes, who is funded by CRUK . They did not have a role in the interpretation of the data or in writing the manuscript.
Funding Information:
ABC-02 was an investigator-initiated study sponsored by UCL, funded by CRUK (funding reference number C1813/A4853) with gemcitabine provided by Lilly Oncology (unrestricted grant). Cancer Research UK was not involved in the design of the current study. They did fund the data collection for ABC-02 and analysis was performed by Andre Lopes, who is funded by CRUK. They did not have a role in the interpretation of the data or in writing the manuscript. BT22 was an Eli Lilly Japan-sponsored trial; Eli Lilly were not involved in the design of the current study. They did fund the data collection for BT22. They did not have a role in the analysis, interpretation of the data or in writing the manuscript. The ABC and TACTIC trials were Australasian Gastro Intestinal Trials Group trials funded in part by grants from Eli Lilly and Amgen, respectively, and the AGITG; additional data collection for PFS and OS was investigator-initiated and supported by the Ministry of Health, Labour, and Welfare, Health Labour Sciences Research Grant (with data transfer to CRUK & UCL CTC under a study-specific agreement). The funders were not involved in the design of the current study. They did fund the data collection for the ABC, TACTIC and AGITG studies. They did not have a role in the analysis, interpretation of the data or in writing the manuscript. JB is partly supported by the UCLH/UCL Biomedical Research Centre. The funders were not involved in the design of the current study. They did fund JB whose author contribution is described below. They did not have a role in the analysis, interpretation of the data or in writing the manuscript. AL is supported by a CRUK grant C444/A15953 to the CRUK & UCL CTC. Cancer Research UK were not involved in the design of the current study. They did fund the data collection for ABC-02 and analysis was performed by Andre Lopes, who is funded by CRUK. They did not have a role in the interpretation of the data or in writing the manuscript.
Publisher Copyright:
© 2020 European Association for the Study of the Liver
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Biliary tract cancer
KW - First-line clinical trials
KW - Landmark survival
KW - Overall survival
KW - Primary site
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U2 - 10.1016/j.jhep.2020.05.014
DO - 10.1016/j.jhep.2020.05.014
M3 - Article
C2 - 32446715
AN - SCOPUS:85089859916
SN - 0168-8278
VL - 73
SP - 1109
EP - 1117
JO - Journal of hepatology
JF - Journal of hepatology
IS - 5
ER -