PICCA study: panitumumab in combination with cisplatin/gemcitabine chemotherapy in KRAS wild-type patients with biliary cancer-a randomised biomarker-driven clinical phase II AIO study.

Autor: Vogel A; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: vogel.arndt@mh-hannover.de., Kasper S; Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany., Bitzer M; Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany., Block A; Department of Medical Oncology and Hematology, University Cancer Center Hamburg, University Hamburg-Eppendorf, Hamburg, Germany., Sinn M; Department of Hematology and Oncology, University Hospital Charité, Berlin, Germany., Schulze-Bergkamen H; National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany., Moehler M; Department of Gastroenterology, Johannes-Gutenberg University, Mainz, Germany., Pfarr N; Institute of Pathology, University Hospital and National Center for Tumor Diseases Heidelberg, Germany; Institute of Pathology, Technical University Munich, Munich, Germany., Endris V; Institute of Pathology, University Hospital and National Center for Tumor Diseases Heidelberg, Germany., Goeppert B; Institute of Pathology, University Hospital and National Center for Tumor Diseases Heidelberg, Germany., Merx K; Interdisziplinären Tumorzentrum Mannheim, Mannheim, Germany., Schnoy E; Department of Internal Medicine, University Hospital Regensburg, Germany, Regensburg, Germany., Siveke JT; 2nd Department of Internal Medicine, Technical University, Munich, Germany., Michl P; Department of Gastroenterology, Philipps-University Marburg, Marburg, Germany., Waldschmidt D; Department of Gastroenterology and Hepatology, University of Cologne, Cologne, Germany., Kuhlmann J; Department of Medicine II, University Hospital Freiburg, Freiburg, Germany., Geissler M; Department of Gastroenterology and Oncology, Klinikum Esslingen, Esslingen, Germany., Kahl C; Department of Hematology, Oncology and Palliative Care, Klinikum Magdeburg, Magdeburg, Germany., Evenkamp R; Lindenallee 53b, 59174 Kamen, Germany., Schmidt T; Gottfried Wilhelm Leibniz University Hannover, Center for Health Economics Research Hannover, Germany., Kuhlmann A; Gottfried Wilhelm Leibniz University Hannover, Center for Health Economics Research Hannover, Germany., Weichert W; 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., Kubicka S; Cancer Center Reutlingen, Reutlingen, Germany.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2018 Mar; Vol. 92, pp. 11-19. Date of Electronic Publication: 2018 Feb 03.
DOI: 10.1016/j.ejca.2017.12.028
Abstrakt: 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/m 2 and gemcitabine 1000 mg/m 2 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.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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