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 Mar;92:11-19. doi: 10.1016/j.ejca.2017.12.028. Epub 2018 Feb 3.

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: Bilary cancer; Chemotherapy; EGFR; Genetic profiling; KRAS; Panitumumab.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / genetics
  • Biliary Tract Neoplasms / mortality
  • Biliary Tract Neoplasms / pathology
  • Biomarkers, Tumor / genetics*
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gemcitabine
  • 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

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • KRAS protein, human
  • Deoxycytidine
  • Panitumumab
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Proto-Oncogene Proteins p21(ras)
  • Cisplatin
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT01320254