Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer

L H Jensen; J Lindebjerg; J Ploen; T F Hansen; A Jakobsen

doi:10.1093/annonc/mds008

Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer

Ann Oncol. 2012 Sep;23(9):2341-2346. doi: 10.1093/annonc/mds008. Epub 2012 Feb 23.

Authors

L H Jensen¹, J Lindebjerg², J Ploen³, T F Hansen³, A Jakobsen³

Affiliations

¹ Departments of Oncology. Electronic address: Lars.Henrik.Jensen@SLB.Regionsyddanmark.dk.
² Pathology, Danish Colorectal Cancer Group South, Vejle Hospital, Vejle and University of Southern Denmark, Odense, Denmark.
³ Departments of Oncology.

PMID: 22367707
DOI: 10.1093/annonc/mds008

Abstract

Background: Combination chemotherapy has proven beneficial in biliary tract cancer and further improvements may be achieved by individualizing treatment based on biomarkers and by adding biological agents. We report the effect of chemotherapy with panitumumab as first-line therapy for KRAS wild-type irresectable biliary tract cancer.

Patients and methods: Patients were treated with gemcitabine 1000 mg/m(2), oxaliplatin 60 mg/m(2), and panitumumab 6 mg/kg i.v. every 2 weeks followed by two daily administrations of capecitabine 1000 mg/m(2) in 7 days.

Results: During 22 months, 46 patients were included in a single institution. The primary end point, fraction of progression-free survival (PFS) at 6 months, was 31/42 [74%; 95% confidence interval (CI) 58% to 84%]. Forty-two patients had measurable disease. Response rate was 33% and disease control rate 86%. Median PFS was 8.3 months (95% CI 6.7-8.7 months) and median overall survival was 10.0 months (95% CI 7.4-12.7 months). Toxicity was manageable including eight cases of epidermal growth factor receptor-related skin adverse events of grade 2 or more.

Conclusions: Marker-driven patient selection is feasible in the systemic treatment of biliary tract cancer. Combination chemotherapy with panitumumab in patients with KRAS wild-type tumors met the efficacy criteria for future testing in a randomized trial.

Trial registration: ClinicalTrials.gov NCT00779454.

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Biliary Tract Neoplasms / drug therapy*
Biliary Tract Neoplasms / metabolism
Biliary Tract Neoplasms / mortality
Biomarkers, Tumor / metabolism*
Capecitabine
Cholangiocarcinoma / drug therapy*
Cholangiocarcinoma / metabolism
Cholangiocarcinoma / mortality
Deoxycytidine / administration & dosage
Deoxycytidine / analogs & derivatives
Disease-Free Survival
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / metabolism
Female
Fluorouracil / administration & dosage
Fluorouracil / analogs & derivatives
Gemcitabine
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Organoplatinum Compounds / administration & dosage
Oxaliplatin
Panitumumab
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins p21(ras)
Statistics, Nonparametric
Treatment Outcome
ras Proteins / genetics*

Substances

Antibodies, Monoclonal
Biomarkers, Tumor
KRAS protein, human
Organoplatinum Compounds
Proto-Oncogene Proteins
Oxaliplatin
Deoxycytidine
Capecitabine
Panitumumab
ErbB Receptors
Proto-Oncogene Proteins p21(ras)
ras Proteins
Fluorouracil
Gemcitabine

Associated data

ClinicalTrials.gov/NCT00779454