Randomized Phase II trial of combination chemotherapy with panitumumab or bevacizumab for patients with inoperable biliary tract cancer without KRAS exon 2 mutations

Research output: Contribution to journalArticle

Abstract

Biliary tract cancers (BTC) are rare and often diagnosed in late stages with advanced, nonresectable disease. The targeted agents panitumumab and bevacizumab have shown promising outcomes in combination with chemotherapy in other gastrointestinal (GI) cancers. We wanted to investigate if panitumumab or bevacizumab was the most promising drug to add to chemotherapy. Eighty-eight patients were randomized to combination chemotherapy supplemented by either panitumumab 6 mg/kg or bevacizumab 10 mg/kg on Day 1 in Arm A and Arm B, respectively. All patients received gemcitabine 1000 mg/m2 on Day 1, oxaliplatin 60 mg/m2 on Day 1 and capecitabine 1000 mg/m2 twice daily from Days 1 to 7. Treatment was repeated every 2 weeks until progression or for a maximum of 6 months. At progression, crossover was made to the other treatment arm. The primary endpoint was progression-free survival (PFS) at 6 months. With 19 of 45 in Arm A and 23 of 43 in Arm B PFS at 6 months, the primary endpoint was not met. The overall response rate (ORR) was 45% vs 20% (P =.03), median PFS was 6.1 months vs 8.2 months (P =.13) and median overall survival (OS) was 9.5 months vs 12.3 months (P =.47) in Arm A and Arm B, respectively. Our study showed no consistent differences between adding panitumumab or bevacizumab to chemotherapy in nonresectable BTC and none of the two regimens qualify for testing in Phase III. However, we found a higher response rate in the panitumumab arm with potential implication for future trials in the neoadjuvant setting.

Details

Authors
  • Nadia Emad Lotfi Amin
  • Torben Frøstrup Hansen
  • Eva Fernebro
  • John Ploen
  • Jakob Eberhard
  • Jan Lindebjerg
  • Lars Henrik Jensen
Organisations
External organisations
  • University of Southern Denmark
  • Växjö Central Hospital
  • Vejle Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • bevacizumab, biliary tract cancer, biological agents, chemotherapy, cholangiocarcinoma, KRAS, panitumumab, targeted therapy
Original languageEnglish
Pages (from-to)119-126
Number of pages8
JournalInternational Journal of Cancer
Volume149
Issue number1
Early online date2021 Feb 9
Publication statusPublished - 2021 Jul 1
Publication categoryResearch
Peer-reviewedYes