TY - JOUR

T1 - PICCA study

T2 - 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, Ralf

AU - Schmidt, Torben

AU - Kuhlmann, Alexander

AU - Weichert, Wilko

AU - Kubicka, Stefan

N1 - Funding Information: This study was supported by Amgen. Dr. Weichert reports personal fees from MSD, BMS, Novartis, Boehringer and Pfizer, grants and personal fees from Roche and AZ, grants from Bruker, outside the submitted work.

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 - Bilary cancer

KW - Chemotherapy

KW - EGFR

KW - Genetic profiling

KW - KRAS

KW - Panitumumab

UR - http://www.scopus.com/inward/record.url?scp=85041568440&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2017.12.028

DO - 10.1016/j.ejca.2017.12.028

M3 - Article

C2 - 29413685

AN - SCOPUS:85041568440

VL - 92

SP - 11

EP - 19

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -