BACKGROUND: Two recent studies (ABC-02 [UK] and BT22 [Japan]) have demonstrated the superiority of cisplatin and gemcitabine (CisGem) chemotherapy over gemcitabine (Gem) alone for patients with pathologically proven advanced biliary tract cancer (BTC: cholangiocarcinoma, gallbladder and ampullary cancers). This pre-planned analysis evaluates the efficacy of CisGem with increased statistical power. PATIENTS AND METHODS: We carried out a meta-analysis of individual patient-level data of these studies to establish the effect of CisGem versus Gem on progression-free survival (PFS), overall survival (OS) and carried out exploratory subgroup analyses. RESULTS: CisGem demonstrates a significant improvement in PFS [hazard ratio (HR)=0.64, 95% confidence interval (CI) 0.53-0.76, P<0.001] and OS (HR=0.65, 95% CI 0.54-0.78, P<0.001) over Gem. This effect is most marked among patients with good performance status (PS 0-1): HR for PFS is 0.61 (95% CI 0.51-0.74), P<0.001 and OS HR=0.64 (95% CI 0.53-0.77), P<0.001. CisGem resulted in improved PFS and OS for intra- and extra-hepatic cholangiocarcinomas and gallbladder cancer. The treatment effect between UK and Japanese patients was consistent with respect to OS (HR=0.65, 95% CI 0.53-0.79 and 0.65, 95% CI 0.42-1.03, respectively); with similar OS in the combination arms (median 11.7 and 11.1 months, respectively). Subgroups least likely to benefit included patients with ampullary tumours and poor performance status (PS2). CONCLUSIONS: CisGem is the standard of care for the first-line treatment of good-PS patients with advanced BTC regardless of ethnicity. Future studies should aim to enhance the effectiveness of this regimen in the first-line setting, establish the role of subsequent (second-line) therapy and assess the role of rationally developed molecular-targeted therapies.
BACKGROUND: Two recent studies (ABC-02 [UK] and BT22 [Japan]) have demonstrated the superiority of cisplatin and gemcitabine (CisGem) chemotherapy over gemcitabine (Gem) alone for patients with pathologically proven advanced biliary tract cancer (BTC: cholangiocarcinoma, gallbladder and ampullary cancers). This pre-planned analysis evaluates the efficacy of CisGem with increased statistical power. PATIENTS AND METHODS: We carried out a meta-analysis of individual patient-level data of these studies to establish the effect of CisGem versus Gem on progression-free survival (PFS), overall survival (OS) and carried out exploratory subgroup analyses. RESULTS: CisGem demonstrates a significant improvement in PFS [hazard ratio (HR)=0.64, 95% confidence interval (CI) 0.53-0.76, P<0.001] and OS (HR=0.65, 95% CI 0.54-0.78, P<0.001) over Gem. This effect is most marked among patients with good performance status (PS 0-1): HR for PFS is 0.61 (95% CI 0.51-0.74), P<0.001 and OS HR=0.64 (95% CI 0.53-0.77), P<0.001. CisGem resulted in improved PFS and OS for intra- and extra-hepatic cholangiocarcinomas and gallbladder cancer. The treatment effect between UK and Japanese patients was consistent with respect to OS (HR=0.65, 95% CI 0.53-0.79 and 0.65, 95% CI 0.42-1.03, respectively); with similar OS in the combination arms (median 11.7 and 11.1 months, respectively). Subgroups least likely to benefit included patients with ampullary tumours and poor performance status (PS2). CONCLUSIONS: CisGem is the standard of care for the first-line treatment of good-PSpatients with advanced BTC regardless of ethnicity. Future studies should aim to enhance the effectiveness of this regimen in the first-line setting, establish the role of subsequent (second-line) therapy and assess the role of rationally developed molecular-targeted therapies.
Authors: Martha M Kirstein; Steffen Marquardt; Nils Jedicke; Silke Marhenke; Wolfgang Koppert; Michael P Manns; Frank Wacker; Arndt Vogel Journal: J Cancer Res Clin Oncol Date: 2017-06-20 Impact factor: 4.553
Authors: Milind Javle; Maeve Lowery; Rachna T Shroff; Karl Heinz Weiss; Christoph Springfeld; Mitesh J Borad; Ramesh K Ramanathan; Lipika Goyal; Saeed Sadeghi; Teresa Macarulla; Anthony El-Khoueiry; Robin Kate Kelley; Ivan Borbath; Su Pin Choo; Do-Youn Oh; Philip A Philip; Li-Tzong Chen; Thanyanan Reungwetwattana; Eric Van Cutsem; Kun-Huei Yeh; Kristen Ciombor; Richard S Finn; Anuradha Patel; Suman Sen; Dale Porter; Randi Isaacs; Andrew X Zhu; Ghassan K Abou-Alfa; Tanios Bekaii-Saab Journal: J Clin Oncol Date: 2017-11-28 Impact factor: 44.544
Authors: Thuy B Tran; Chinmaya K Bal; Kurt Schaberg; Teri A Longacre; Bhupinder S Chatrath; George A Poultsides Journal: Dig Dis Sci Date: 2015-04-01 Impact factor: 3.199
Authors: Ghassan K Abou-Alfa; Jesper B Andersen; William Chapman; Michael Choti; Stuart J Forbes; Gregory J Gores; Theodore S Hong; James J Harding; Matthew G Vander Heiden; Milind Javle; Robin K Kelley; Lawrence N Kwong; Maeve Lowery; Allyson Merrell; Katsuyuki Miyabe; Andrew Rhim; Supriya Saha; Daniela Sia; Suebpong Tanasanvimon; Alan Venook; Juan W Valle; Chad Walesky; Jonathan Whetstine; Holger Willenbring; Andrew X Zhu; Donna Mayer; Ben Z Stanger Journal: J Gastrointest Oncol Date: 2016-12