Arndt Vogel1, Stefan Kasper2, Michael Bitzer3, Andreas Block4, Marianne Sinn5, Henning Schulze-Bergkamen6, Markus Moehler7, Nicole Pfarr8, Volker Endris9, Benjamin Goeppert9, Kirsten Merx10, Elisabeth Schnoy11, Jens T Siveke12, Patrick Michl13, Dirk Waldschmidt14, Jan Kuhlmann15, Michael Geissler16, Christoph Kahl17, Ralph Evenkamp18, Torben Schmidt19, Alexander Kuhlmann19, Wilko Weichert20, Stefan Kubicka21. 1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: vogel.arndt@mh-hannover.de. 2. Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. 3. Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany. 4. Department of Medical Oncology and Hematology, University Cancer Center Hamburg, University Hamburg-Eppendorf, Hamburg, Germany. 5. Department of Hematology and Oncology, University Hospital Charité, Berlin, Germany. 6. National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany. 7. Department of Gastroenterology, Johannes-Gutenberg University, Mainz, Germany. 8. Institute of Pathology, University Hospital and National Center for Tumor Diseases Heidelberg, Germany; Institute of Pathology, Technical University Munich, Munich, Germany. 9. Institute of Pathology, University Hospital and National Center for Tumor Diseases Heidelberg, Germany. 10. Interdisziplinären Tumorzentrum Mannheim, Mannheim, Germany. 11. Department of Internal Medicine, University Hospital Regensburg, Germany, Regensburg, Germany. 12. 2nd Department of Internal Medicine, Technical University, Munich, Germany. 13. Department of Gastroenterology, Philipps-University Marburg, Marburg, Germany. 14. Department of Gastroenterology and Hepatology, University of Cologne, Cologne, Germany. 15. Department of Medicine II, University Hospital Freiburg, Freiburg, Germany. 16. Department of Gastroenterology and Oncology, Klinikum Esslingen, Esslingen, Germany. 17. Department of Hematology, Oncology and Palliative Care, Klinikum Magdeburg, Magdeburg, Germany. 18. Lindenallee 53b, 59174 Kamen, Germany. 19. Gottfried Wilhelm Leibniz University Hannover, Center for Health Economics Research Hannover, Germany. 20. Institute of Pathology, University Hospital and National Center for Tumor Diseases Heidelberg, Germany; Institute of Pathology, Technical University Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Germany. 21. Cancer Center Reutlingen, Reutlingen, Germany.
Abstract
BACKGROUND: Combination chemotherapy has shown benefit in the treatment of biliary cancer and further improvements might be achieved by the addition of a biological agent. We report here the effect of chemotherapy with the monoclonal EGFR antibody panitumumab as therapy for KRAS wild-type biliary cancer. PATIENTS AND METHODS: Patients with advanced biliary tract cancer were randomised (2:1) to receive cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8/q3w with (arm A) or without panitumumab (arm B; 9 mg/kg BW, i.v q3w). The primary end-point was the evaluation of progression-free survival (PFS) at 6 months. Secondary end-points included objective response rate (ORR), overall survival (OS), and toxicity. In addition, a post hoc assessment of genetic alterations was performed. Finally, we performed a meta-analysis of trials with chemotherapy with and without EGFR antibodies. RESULTS: Sixty-two patients were randomised in arm A and 28 patients in arm B. Patients received 7 treatment cycles in median (1-35) with a median treatment duration of 4.7 months (141 days, 8-765). PFS rate at 6 months was 54% in patients treated with cisplatin/gemcitabine and panitumumab but was 73% in patients treated with cisplatin/gemcitabine without antibody, respectively. Secondary end-points were an ORR of 45% in treatment arm A compared with 39% receiving treatment B and a median OS of 12.8 months (arm A) and of 20.1 months (arm B), respectively. In contrast to the p53-status, genetic alterations in IDH1/2 were linked to a high response after chemotherapy and prolonged survival. In accordance with our results, the meta-analysis of 12 trials did not reveal a survival advantage for patients treated with EGFR antibodies compared with chemotherapy alone. CONCLUSIONS: Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. Genetic profiling should be included in CCA trials to identify and validate predictive and prognostic biomarkers. CLINICAL TRIALS NUMBER: The trial was registered with NCT01320254.
BACKGROUND: Combination chemotherapy has shown benefit in the treatment of biliary cancer and further improvements might be achieved by the addition of a biological agent. We report here the effect of chemotherapy with the monoclonal EGFR antibody panitumumab as therapy for KRAS wild-type biliary cancer. PATIENTS AND METHODS: Patients with advanced biliary tract cancer were randomised (2:1) to receive cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8/q3w with (arm A) or without panitumumab (arm B; 9 mg/kg BW, i.v q3w). The primary end-point was the evaluation of progression-free survival (PFS) at 6 months. Secondary end-points included objective response rate (ORR), overall survival (OS), and toxicity. In addition, a post hoc assessment of genetic alterations was performed. Finally, we performed a meta-analysis of trials with chemotherapy with and without EGFR antibodies. RESULTS: Sixty-two patients were randomised in arm A and 28 patients in arm B. Patients received 7 treatment cycles in median (1-35) with a median treatment duration of 4.7 months (141 days, 8-765). PFS rate at 6 months was 54% in patients treated with cisplatin/gemcitabine and panitumumab but was 73% in patients treated with cisplatin/gemcitabine without antibody, respectively. Secondary end-points were an ORR of 45% in treatment arm A compared with 39% receiving treatment B and a median OS of 12.8 months (arm A) and of 20.1 months (arm B), respectively. In contrast to the p53-status, genetic alterations in IDH1/2 were linked to a high response after chemotherapy and prolonged survival. In accordance with our results, the meta-analysis of 12 trials did not reveal a survival advantage for patients treated with EGFR antibodies compared with chemotherapy alone. CONCLUSIONS: Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. Genetic profiling should be included in CCA trials to identify and validate predictive and prognostic biomarkers. CLINICAL TRIALS NUMBER: The trial was registered with NCT01320254.
Authors: Avani Athauda; Caroline Fong; David K Lau; Milind Javle; Ghassan K Abou-Alfa; Chigusa Morizane; Keith Steward; Ian Chau Journal: Cancer Treat Rev Date: 2020-03-12 Impact factor: 12.111