Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival data
Background & Aims: Gemcitabine/cisplatin (GemCis) was the long-standing first-line treatment for advanced biliary tract cancers (BTCs). Following positive results from the TOPAZ-01 and KEYNOTE-966 trials, immune checkpoint inhibitors (ICIs) combined with chemotherapy are now the standard of...
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Elsevier
2025-03-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555924002945 |
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| author | Zhihao Li Daniel Aliseda Owen Jones Luckshi Rajendran Christian Magyar Robert Grant Grainne M. O’Kane Anna Saborowski Gonzalo Sapisochin Arndt Vogel |
| author_facet | Zhihao Li Daniel Aliseda Owen Jones Luckshi Rajendran Christian Magyar Robert Grant Grainne M. O’Kane Anna Saborowski Gonzalo Sapisochin Arndt Vogel |
| author_sort | Zhihao Li |
| collection | DOAJ |
| description | Background & Aims: Gemcitabine/cisplatin (GemCis) was the long-standing first-line treatment for advanced biliary tract cancers (BTCs). Following positive results from the TOPAZ-01 and KEYNOTE-966 trials, immune checkpoint inhibitors (ICIs) combined with chemotherapy are now the standard of care. We aim to compare the efficacy of first-line therapies for advanced BTCs. Methods: Our systematic review included studies from five databases focusing on English-language articles published between January 2010 and June 2024. We included randomized clinical trials (RCTs) that featured GemCis in a treatment arm for treatment-naive adults with advanced BTCs. The primary endpoints were overall survival (OS) and progression-free survival. We conducted a one-stage meta-analysis using reconstructed survival data, Cox-based models, and restricted mean survival time (RMST). Results: After screening 8,797 studies, 17 RCTs were selected, involving a total of 4,584 patients. Of these, 2,140 (46.7%) received GemCis. The majority (68.9%) were diagnosed with intrahepatic or extrahepatic cholangiocarcinoma, and 80% had metastatic disease at the time of treatment. The pooled median OS in the GemCis group was 11.6 months (95% CI 11.3–12.2 months). GemCis plus pembrolizumab (hazard ratio [HR] 0.99, 95% CI 0.98–0.99; p <0.001), GemCis plus durvalumab (HR 0.98, 95% CI 0.97–0.99; p = 0.015), GemCis plus S-1 (HR 0.97 95% CI 0.95–0.99; p <0.001), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.98–0.99; p <0.001) demonstrated superior OS compared with GemCis alone. These combinations also showed increases in RMST by +1.1, +2.5, +2.8, and +2.1 months, respectively. In terms of progression-free survival, GemCis with ICIs (HR 0.91, 95% CI 0.78–0.94; p <0.001), GemCis plus S-1 (HR 0.98, 95% CI 0.96–0.99; p = 0.003), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.97–0.99; p <0.001) also demonstrated superiority, with corresponding RMST increases of +0.7, +1.9, and +2.5 months, respectively. Conclusions: Despite incremental advancements, a breakthrough in advanced BTC treatment remains elusive. Further improvements in treatment efficacy may require biomarker identification to optimize combinational therapies for better patient selection. Impact and implications: This study analyzed recent RCTs, including KEYNOTE-966, TOPAZ-1, NIFE, and SWOG 1815, involving 4,584 patients with advanced biliary tract cancer. A meta-analysis of 17 treatment arms, using reconstructed survival data, confirmed the modest survival benefit of GemCis plus ICIs, supporting its guideline adoption. The findings, however, highlight the need for biomarker identification and better patient selection. |
| format | Article |
| id | doaj-art-11cfa34c53c04099a5e94bc256c9fd92 |
| institution | Kabale University |
| issn | 2589-5559 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj-art-11cfa34c53c04099a5e94bc256c9fd922025-02-03T04:16:51ZengElsevierJHEP Reports2589-55592025-03-0173101290Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival dataZhihao Li0Daniel Aliseda1Owen Jones2Luckshi Rajendran3Christian Magyar4Robert Grant5Grainne M. O’Kane6Anna Saborowski7Gonzalo Sapisochin8Arndt Vogel9HBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, CanadaHBP and Liver Transplant Unit, Clinica Universidad de Navarra, University of Navarra, Pamplona-Madrid, SpainHBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, CanadaHBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, CanadaHBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, CanadaDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, CanadaWallace McCain Centre for Pancreatic Cancer, Princess Margaret Hospital, Toronto, ON, Canada; Department of Medical Oncology, St Vincent’s University Hospital and University College Dublin, Dublin, IrelandDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, GermanyHBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, CanadaDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; Division of Gastroenterology and Hepatology, University Health Network, Toronto, ON, Canada; Corresponding author. Address: Division of Gastroenterology and Hepatology, University Health Network, Toronto, ON, Canada.Background & Aims: Gemcitabine/cisplatin (GemCis) was the long-standing first-line treatment for advanced biliary tract cancers (BTCs). Following positive results from the TOPAZ-01 and KEYNOTE-966 trials, immune checkpoint inhibitors (ICIs) combined with chemotherapy are now the standard of care. We aim to compare the efficacy of first-line therapies for advanced BTCs. Methods: Our systematic review included studies from five databases focusing on English-language articles published between January 2010 and June 2024. We included randomized clinical trials (RCTs) that featured GemCis in a treatment arm for treatment-naive adults with advanced BTCs. The primary endpoints were overall survival (OS) and progression-free survival. We conducted a one-stage meta-analysis using reconstructed survival data, Cox-based models, and restricted mean survival time (RMST). Results: After screening 8,797 studies, 17 RCTs were selected, involving a total of 4,584 patients. Of these, 2,140 (46.7%) received GemCis. The majority (68.9%) were diagnosed with intrahepatic or extrahepatic cholangiocarcinoma, and 80% had metastatic disease at the time of treatment. The pooled median OS in the GemCis group was 11.6 months (95% CI 11.3–12.2 months). GemCis plus pembrolizumab (hazard ratio [HR] 0.99, 95% CI 0.98–0.99; p <0.001), GemCis plus durvalumab (HR 0.98, 95% CI 0.97–0.99; p = 0.015), GemCis plus S-1 (HR 0.97 95% CI 0.95–0.99; p <0.001), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.98–0.99; p <0.001) demonstrated superior OS compared with GemCis alone. These combinations also showed increases in RMST by +1.1, +2.5, +2.8, and +2.1 months, respectively. In terms of progression-free survival, GemCis with ICIs (HR 0.91, 95% CI 0.78–0.94; p <0.001), GemCis plus S-1 (HR 0.98, 95% CI 0.96–0.99; p = 0.003), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.97–0.99; p <0.001) also demonstrated superiority, with corresponding RMST increases of +0.7, +1.9, and +2.5 months, respectively. Conclusions: Despite incremental advancements, a breakthrough in advanced BTC treatment remains elusive. Further improvements in treatment efficacy may require biomarker identification to optimize combinational therapies for better patient selection. Impact and implications: This study analyzed recent RCTs, including KEYNOTE-966, TOPAZ-1, NIFE, and SWOG 1815, involving 4,584 patients with advanced biliary tract cancer. A meta-analysis of 17 treatment arms, using reconstructed survival data, confirmed the modest survival benefit of GemCis plus ICIs, supporting its guideline adoption. The findings, however, highlight the need for biomarker identification and better patient selection.http://www.sciencedirect.com/science/article/pii/S2589555924002945Biliary tract cancersCholangiocarcinomaSystemic therapyFirst-line therapyImmunotherapySystematic review |
| spellingShingle | Zhihao Li Daniel Aliseda Owen Jones Luckshi Rajendran Christian Magyar Robert Grant Grainne M. O’Kane Anna Saborowski Gonzalo Sapisochin Arndt Vogel Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival data JHEP Reports Biliary tract cancers Cholangiocarcinoma Systemic therapy First-line therapy Immunotherapy Systematic review |
| title | Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival data |
| title_full | Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival data |
| title_fullStr | Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival data |
| title_full_unstemmed | Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival data |
| title_short | Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival data |
| title_sort | recent advances in systemic therapy for advanced biliary tract cancer a systematic review and meta analysis using reconstructed rct survival data |
| topic | Biliary tract cancers Cholangiocarcinoma Systemic therapy First-line therapy Immunotherapy Systematic review |
| url | http://www.sciencedirect.com/science/article/pii/S2589555924002945 |
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