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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

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

in: EUR J CANCER, Jahrgang 92, 03.2018, S. 11-19.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Vogel, A, Kasper, S, Bitzer, M, Block, A, Sinn, M, Schulze-Bergkamen, H, Moehler, M, Pfarr, N, Endris, V, Goeppert, B, Merx, K, Schnoy, E, Siveke, JT, Michl, P, Waldschmidt, D, Kuhlmann, J, Geissler, M, Kahl, C, Evenkamp, R, Schmidt, T, Kuhlmann, A, Weichert, W & Kubicka, S 2018, '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', EUR J CANCER, Jg. 92, S. 11-19. https://doi.org/10.1016/j.ejca.2017.12.028

APA

Vogel, A., Kasper, S., Bitzer, M., Block, A., Sinn, M., Schulze-Bergkamen, H., Moehler, M., Pfarr, N., Endris, V., Goeppert, B., Merx, K., Schnoy, E., Siveke, J. T., Michl, P., Waldschmidt, D., Kuhlmann, J., Geissler, M., Kahl, C., Evenkamp, R., ... Kubicka, S. (2018). 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. EUR J CANCER, 92, 11-19. https://doi.org/10.1016/j.ejca.2017.12.028

Vancouver

Vogel A, Kasper S, Bitzer M, Block A, Sinn M, Schulze-Bergkamen H et al. 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. EUR J CANCER. 2018 Mär;92:11-19. https://doi.org/10.1016/j.ejca.2017.12.028

Bibtex

@article{e1164fd5eefd4fb1a1a300f16918b91d,
title = "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",
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.",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Biliary Tract Neoplasms/drug therapy, Biomarkers, Tumor/genetics, Cisplatin/administration & dosage, Deoxycytidine/administration & dosage, Disease Progression, Disease-Free Survival, Female, Gene Expression Profiling/methods, Germany, Humans, Isocitrate Dehydrogenase/genetics, Kaplan-Meier Estimate, Male, Middle Aged, Mutation, Panitumumab, Precision Medicine, Proto-Oncogene Proteins p21(ras)/genetics, Risk Factors, Time Factors, Treatment Outcome, Young Adult",
author = "Arndt Vogel and Stefan Kasper and Michael Bitzer and Andreas Block and Marianne Sinn and Henning Schulze-Bergkamen and Markus Moehler and Nicole Pfarr and Volker Endris and Benjamin Goeppert and Kirsten Merx and Elisabeth Schnoy and Siveke, {Jens T} and Patrick Michl and Dirk Waldschmidt and Jan Kuhlmann and Michael Geissler and Christoph Kahl and Ralph Evenkamp and Torben Schmidt and Alexander Kuhlmann and Wilko Weichert and Stefan Kubicka",
note = "Copyright {\textcopyright} 2018 Elsevier Ltd. All rights reserved.",
year = "2018",
month = mar,
doi = "10.1016/j.ejca.2017.12.028",
language = "English",
volume = "92",
pages = "11--19",
journal = "EUR J CANCER",
issn = "0959-8049",
publisher = "Elsevier Limited",

}

RIS

TY - JOUR

T1 - 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

AU - Vogel, Arndt

AU - Kasper, Stefan

AU - Bitzer, Michael

AU - Block, Andreas

AU - Sinn, Marianne

AU - Schulze-Bergkamen, Henning

AU - Moehler, Markus

AU - Pfarr, Nicole

AU - Endris, Volker

AU - Goeppert, Benjamin

AU - Merx, Kirsten

AU - Schnoy, Elisabeth

AU - Siveke, Jens T

AU - Michl, Patrick

AU - Waldschmidt, Dirk

AU - Kuhlmann, Jan

AU - Geissler, Michael

AU - Kahl, Christoph

AU - Evenkamp, Ralph

AU - Schmidt, Torben

AU - Kuhlmann, Alexander

AU - Weichert, Wilko

AU - Kubicka, Stefan

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Monoclonal/administration & dosage

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Biliary Tract Neoplasms/drug therapy

KW - Biomarkers, Tumor/genetics

KW - Cisplatin/administration & dosage

KW - Deoxycytidine/administration & dosage

KW - Disease Progression

KW - Disease-Free Survival

KW - Female

KW - Gene Expression Profiling/methods

KW - Germany

KW - Humans

KW - Isocitrate Dehydrogenase/genetics

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Mutation

KW - Panitumumab

KW - Precision Medicine

KW - Proto-Oncogene Proteins p21(ras)/genetics

KW - Risk Factors

KW - Time Factors

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1016/j.ejca.2017.12.028

DO - 10.1016/j.ejca.2017.12.028

M3 - SCORING: Journal article

C2 - 29413685

VL - 92

SP - 11

EP - 19

JO - EUR J CANCER

JF - EUR J CANCER

SN - 0959-8049

ER -