Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: A multicenter, randomized phase IIb study

Beate Schultheis, D. Reuter, M. P. Ebert, J. Siveke, A. Kerkhoff, W. E. Berdel, R. Hofheinz, D. M. Behringer, W. E. Schmidt, E. Goker, S. De Dosso, M. Kneba, S. Yalcin, F. Overkamp, F. Schlegel, M. Dommach, R. Rohrberg, T. Steinmetz, M. Bulitta, D. Strumberg

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115 Scopus citations

Abstract

Background: This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus placebo as first-line therapy in patients with advanced pancreatic cancer. Patients and methods: Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary end point was overall survival (OS), secondary end points included time to progression, overall response rate, safety and quality of life. Results: A total of 192 patients were randomized, with 186 of them being assessable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared with 19%/10% for gem plus placebo (HR = 0.69; P = 0.03/HR = 0.68; P = 0.02). Median OS/PFS was 8.6/5.1 months for gem plus nimo versus 6.0/3.4 mo in the gem plus placebo group (HR = 0.69; P = 0.0341/HR = 0.68; P = 0.0163), with very few grade 3/4 toxicities. KRAS wildtype patients experienced a significantly better OS than those with KRAS mutations (11.6 versus 5.6 months, P = 0.03). Conclusion: This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially, those patients with KRAS wildtype seem to benefit.

Original languageEnglish
Pages (from-to)2429-2435
Number of pages7
JournalAnnals of Oncology
Volume28
Issue number10
DOIs
StatePublished - Oct 2017

Keywords

  • EGFR inhibitor
  • Gemcitabine
  • KRAS wildtype
  • Nimotuzumab
  • Pancreatic cancer

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