Stefano Cascinu1, Rossana Berardi2, Alberto Sobrero3, Paolo Bidoli4, Roberto Labianca5, Salvatore Siena6, Daris Ferrari7, Sandro Barni8, Enrico Aitini9, Vittorina Zagonel10, Francesco Caprioni3, Federica Villa4, Stefania Mosconi5, Luca Faloppi2, Giuseppe Tonini11, Corrado Boni12, Pierfranco Conte13, Francesco Di Costanzo14, Michela Cinquini15. 1. Medical Oncology Unit, Università Politecnica delle Marche, Ospedali Riuniti di Ancona, Ancona, Italy. Electronic address: cascinu@yahoo.com. 2. Medical Oncology Unit, Università Politecnica delle Marche, Ospedali Riuniti di Ancona, Ancona, Italy. 3. Medical Oncology Unit, Ospedale S. Martino, Genova, Italy. 4. Medical Oncology Unit, Ospedale S. Gerardo, Monza, Italy. 5. Medical Oncology Unit, Ospedali Riuniti, Bergamo, Italy. 6. Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy. 7. Medical Oncology Unit, Ospedale S. Paolo, Milano, Italy. 8. Medical Oncology Unit, Treviglio Hospital, Treviglio, Italy. 9. Medical Oncology Unit, C. Poma Hospital, Mantova, Italy. 10. Medical Oncology Unit, Istituto Oncologico Veneto, Padova, Italy. 11. Medical Oncology Unit, University Campus Bio-Medico, Rome, Italy. 12. Medical Oncology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy. 13. Medical Oncology Unit, Policlinico Universitario, Modena, Italy. 14. Medical Oncology Unit Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy. 15. New Drug Development Strategies Laboratory, Mario Negri Institute, Milano, Italy.
Abstract
BACKGROUND: The RAF-MEK-ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations. A phase II randomized trial was designed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer. METHODS:Locally advanced or metastatic pancreatic adenocarcinoma patients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400mg bid (arm A) or without sorafenib (arm B). RESULTS: One hundred and fourteen patients were enrolled; of these, 43 (74.6%) patients progressed in arm A and 44 (82.4%) in arm B. Median progression-free survival was 4.3 months (95% CI: 2.7-6.5) and 4.5 months (95% CI: 2.5-5.2), respectively (HR=0.92; 95% CI: 0.62-1.35). Median overall survival was 7.5 (95% CI: 5.6-9.7) and 8.3 months (95% CI: 6.2-8.7), respectively (HR=0.95; 95% CI: 0.62-1.48). Response rates were 3.4% in arm A and 3.6% in arm B. CONCLUSIONS:Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients, and therefore should not be assessed in phase III trials.
RCT Entities:
BACKGROUND: The RAF-MEK-ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations. A phase II randomized trial was designed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer. METHODS: Locally advanced or metastatic pancreatic adenocarcinomapatients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400mg bid (arm A) or without sorafenib (arm B). RESULTS: One hundred and fourteen patients were enrolled; of these, 43 (74.6%) patients progressed in arm A and 44 (82.4%) in arm B. Median progression-free survival was 4.3 months (95% CI: 2.7-6.5) and 4.5 months (95% CI: 2.5-5.2), respectively (HR=0.92; 95% CI: 0.62-1.35). Median overall survival was 7.5 (95% CI: 5.6-9.7) and 8.3 months (95% CI: 6.2-8.7), respectively (HR=0.95; 95% CI: 0.62-1.48). Response rates were 3.4% in arm A and 3.6% in arm B. CONCLUSIONS:Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancerpatients, and therefore should not be assessed in phase III trials.
Authors: Andrea Wang-Gillam; Kian-Huat Lim; Hongmei Jiang; Mai Xu; Lin Li; Patrick Grierson; Paarth Dodhiawala; Maureen Highkin; Daoxiang Zhang; Qiong Li Journal: Mol Cancer Ther Date: 2018-07-31 Impact factor: 6.261
Authors: Sandeep Kumar; Joseph R Inigo; Rahul Kumar; Ajay K Chaudhary; Jordan O'Malley; Srimmitha Balachandar; Jianmin Wang; Kristopher Attwood; Neelu Yadav; Steven Hochwald; Xinjiang Wang; Dhyan Chandra Journal: Cancer Lett Date: 2017-10-26 Impact factor: 8.679