John Bridgewater1, Peter Fletcher2, Daniel H Palmer3, Hassan Z Malik4, Raj Prasad5, Darius Mirza6, Alan Anthony5, Pippa Corrie7, Stephen Falk8, Meg Finch-Jones8, Harpreet Wasan9, Paul Ross10, Lucy Wall11, Jonathan Wadsley12, Thomas R Evans13, Deborah Stocken14, Clive Stubbs2, Raaj Praseedom15, Yuk Ting Ma16, Brian Davidson17, John Neoptolemos18, Tim Iveson19, David Cunningham20, O James Garden21, Juan W Valle22, John Primrose23. 1. UCL Cancer Institute, London, United Kingdom. 2. Cancer Clinical Trials Unit, Birmingham, United Kingdom. 3. Molecular and Clinical Cancer Medicine, Liverpool, United Kingdom. 4. University Hospital Aintree, Liverpool, United Kingdom. 5. Leeds Teaching Hospital NHS Trust, Leeds, United Kingdom. 6. Birmingham Woman's and Children's NHS Trust, Birmingham, United Kingdom. 7. Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom. 8. University Hospitals Bristol NHS Trust, Bristol, United Kingdom. 9. Imperial College Healthcare NHS Trust, London, United Kingdom. 10. Guys and St Thomas's NHS Trust, London, United Kingdom. 11. Western General Hospital, Edinburgh, United Kingdom. 12. Weston Park Cancer Centre, Sheffield, United Kingdom. 13. University of Glasgow, Glasgow, United Kingdom. 14. Leeds Institute of Clinical Trials Research, Leeds, United Kingdom. 15. Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. 16. Institute of Immunology and Immunotherapy, Birmingham, United Kingdom. 17. Royal Free Hospital NHS Trust, London, United Kingdom. 18. University of Heidelberg, Heidelberg, Germany. 19. University Hospital Southampton NHS Trust, Southampton, United Kingdom. 20. Royal Marsden Hospital, London, United Kingdom. 21. University of Edinburgh, Edinburgh, United Kingdom. 22. University of Manchester, Manchester, United Kingdom. 23. University of Southampton, Southampton, United Kingdom.
Abstract
PURPOSE: The BILCAP study described a modest benefit for capecitabine as adjuvant therapy for curatively resected biliary tract cancer (BTC), and capecitabine has become the standard of care. We present the long-term data and novel exploratory subgroup analyses. METHODS: This randomized, controlled, multicenter, phase III study recruited patients age 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent and an Eastern Cooperative Oncology Group performance status of < 2. Patients were randomly assigned 1:1 to receive oral capecitabine (1,250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation. The primary outcome was overall survival (OS). This study is registered with EudraCT 2005-003318-13. RESULTS: Between March 15, 2006, and December 4, 2014, 447 patients were enrolled; 223 patients with BTC resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. At the data cutoff of January 21, 2021, the median follow-up for all patients was 106 months (95% CI, 98 to 108). In the intention-to-treat analysis, the median OS was 49.6 months (95% CI, 35.1 to 59.1) in the capecitabine group compared with 36.1 months (95% CI, 29.7 to 44.2) in the observation group (adjusted hazard ratio 0.84; 95% CI, 0.67 to 1.06). In a protocol-specified sensitivity analysis, adjusting for minimization factors, nodal status, grade, and sex, the OS hazard ratio was 0.74 (95% CI, 0.59 to 0.94). We further describe the prognostic impact of R status, grade, nodal status, and sex. CONCLUSION: This long-term analysis supports the previous analysis, suggesting that capecitabine can improve OS in patients with resected BTC when used as adjuvant chemotherapy after surgery and should be considered as the standard of care.
PURPOSE: The BILCAP study described a modest benefit for capecitabine as adjuvant therapy for curatively resected biliary tract cancer (BTC), and capecitabine has become the standard of care. We present the long-term data and novel exploratory subgroup analyses. METHODS: This randomized, controlled, multicenter, phase III study recruited patients age 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent and an Eastern Cooperative Oncology Group performance status of < 2. Patients were randomly assigned 1:1 to receive oral capecitabine (1,250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation. The primary outcome was overall survival (OS). This study is registered with EudraCT 2005-003318-13. RESULTS: Between March 15, 2006, and December 4, 2014, 447 patients were enrolled; 223 patients with BTC resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. At the data cutoff of January 21, 2021, the median follow-up for all patients was 106 months (95% CI, 98 to 108). In the intention-to-treat analysis, the median OS was 49.6 months (95% CI, 35.1 to 59.1) in the capecitabine group compared with 36.1 months (95% CI, 29.7 to 44.2) in the observation group (adjusted hazard ratio 0.84; 95% CI, 0.67 to 1.06). In a protocol-specified sensitivity analysis, adjusting for minimization factors, nodal status, grade, and sex, the OS hazard ratio was 0.74 (95% CI, 0.59 to 0.94). We further describe the prognostic impact of R status, grade, nodal status, and sex. CONCLUSION: This long-term analysis supports the previous analysis, suggesting that capecitabine can improve OS in patients with resected BTC when used as adjuvant chemotherapy after surgery and should be considered as the standard of care.
Authors: Christoph Roderburg; Tobias Essing; Linde Kehmann; Sarah Krieg; Simon Labuhn; Jennis Kandler; Tom Luedde; Sven H Loosen Journal: Cancers (Basel) Date: 2022-08-21 Impact factor: 6.575