Panitumumab in Combination With Gemcitabine and Oxaliplatin Does Not Prolong Survival in Wild-Type KRAS Advanced Biliary Tract Cancer: A Randomized Phase 2 Trial (Vecti-BIL Study)

Cancer. 2016 Feb 15;122(4):574-81. doi: 10.1002/cncr.29778. Epub 2015 Nov 5.

Abstract

Background: Biliary tract cancer (BTC) is a rare and lethal disease with few therapeutic options. Preclinical data suggest that the epidermal growth factor receptor (EGFR) pathway could be involved in its progression.

Methods: This open-label, randomized phase 2 trial recruited chemotherapy-naive patients with advanced BTC displaying a wild-type (WT) KRAS status. Patients were randomized to gemcitabine (1000 mg/m(2) ) and oxaliplatin (100 mg/m(2) ) with (arm A) or without (arm B) panitumumab (6 mg/kg) for up to 12 cycles. The primary endpoint was progression-free survival (PFS) analyzed in an intention-to-treat fashion.

Results: Eighty-nine patients (45 in arm A and 44 in arm B) were enrolled between June 2010 and September 2013. After a median follow-up of 10.1 months, the median PFS was 5.3 months (95% confidence interval, 3.3-7.2 months) in arm A and 4.4 months (95% confidence interval, 2.6-6.2 months) in arm B (P = .27). No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P = .42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P = .13). As for safety, skin toxicity was the main adverse event in arm A (80% of the patients). A higher incidence of diarrhea (55.5% vs 31.8%), mucositis (22.2% vs 13.6%), and constipation (24.4% vs 15.9%) was seen in arm A.

Conclusions: These results confirm the marginal role of anti-EGFR therapy even for WT KRAS-selected BTC.

Trial registration: ClinicalTrials.gov NCT01389414.

Keywords: KRAS; biliary cancer; chemotherapy; cholangiocarcinoma; gemcitabine and oxaliplatin (GEMOX); panitumumab.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Extrahepatic / pathology*
  • Bile Ducts, Intrahepatic / pathology*
  • Biliary Tract Neoplasms / drug therapy
  • Biliary Tract Neoplasms / genetics
  • Biliary Tract Neoplasms / pathology
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / pathology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • Gallbladder Neoplasms / drug therapy*
  • Gallbladder Neoplasms / genetics
  • Gallbladder Neoplasms / pathology
  • Humans
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Panitumumab
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • KRAS protein, human
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Panitumumab
  • gemcitabine
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)

Associated data

  • ClinicalTrials.gov/NCT01389414