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

verfasst von

Arndt Vogel, Stefan Kasper, Michael Bitzer, Andreas Block, Marianne Sinn, Henning Schulze-Bergkamen, Markus Moehler, Nicole Pfarr, Volker Endris, Benjamin Goeppert, Kirsten Merx, Elisabeth Schnoy, Jens T. Siveke, Patrick Michl, Dirk Waldschmidt, Jan Kuhlmann, Michael Geissler, Christoph Kahl, Ralf Evenkamp, Torben Schmidt, Alexander Kuhlmann, Wilko Weichert, Stefan Kubicka

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.

Organisationseinheit(en)

Institut für Versicherungsbetriebslehre
Center for Health Economics Research Hannover (CHERH)

Externe Organisation(en)

Medizinische Hochschule Hannover (MHH)
Universität Duisburg-Essen
Eberhard Karls Universität Tübingen
Universität Hamburg
Charité - Universitätsmedizin Berlin
Ruprecht-Karls-Universität Heidelberg
Johannes Gutenberg-Universität Mainz
Deutsches Krebsforschungszentrum (DKFZ)
Technische Universität München (TUM)
Mannheim Cancer Center (MCC)
Universität Regensburg
Philipps-Universität Marburg
Universität zu Köln
Universitätsklinikum Freiburg
Klinikum Esslingen
Klinikum Magdeburg
Deutsches Konsortium für Translationale Krebsforschung (DKTK)
Krebszentrum Reutlingen

Typ

Artikel

Journal

European Journal of Cancer

Band

92

Seiten

11-19

Anzahl der Seiten

9

ISSN

0959-8049

Publikationsdatum

03.2018

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Onkologie, Krebsforschung

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1016/j.ejca.2017.12.028 (Zugang: Geschlossen)