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A phase II randomized study of cetuximab and bevacizumab alone or in combination with gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma

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Summary

The purpose of this study was to assess the efficacy and safety of bevacizumab plus cetuximab with or without gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients with locally advanced or metastatic pancreatic adenocarcinoma, previously untreated, were randomized to bevacizumab (10 mg/kg q2w) plus cetuximab (400/250 mg/m2 initial/weekly), either with (Arm A) or without (Arm B) gemcitabine (1000 mg/m2 weekly × 3 of 4 weeks). Tumor assessments were performed q8w. Primary study endpoint was progression-free survival (PFS). Sixty-one patients were randomized to Arm A (n = 30) or Arm B (n = 31). Median treatment duration was 9 weeks in Arm A and 8 weeks in Arm B (range, 2.0–40.4). Patients in Arm A had median PFS and overall survival values of 3.55 months and 5.41 months, respectively, compared to 1.91 months and 4.17 months in Arm B. The study closed early due to lack of sufficient efficacy in both treatment arms. Although both regimens were well tolerated, patients treated with gemcitabine experienced more grade 3–4 toxicities, including proteinuria and thromboembolic events. The combination of cetuximab and bevacizumab did not result in promising activity with or without gemcitabine, suggesting that a strategy of dual EGFR/VEGF inhibition in pancreatic cancer does not warrant further development. To our knowledge, this is one of the first trials to evaluate a completely noncytotoxic regimen in the first-line treatment of advanced pancreatic cancer. (ClinicalTrials.gov number, NCT00326911).

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Acknowledgments

The study was sponsored by ImClone LLC, a wholly-owned subsidiary of Eli Lilly & Co, Bridgewater, New Jersey; and Bristol-Myers Squibb, Princeton, New Jersey.

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Authors and Affiliations

  1. Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, 1600 Divisadero Street, 4th Floor, Box 1705, San Francisco, CA, 94115, USA

    Andrew H. Ko

  2. ImClone Systems LLC, a wholly-owned subsidiary of Eli-Lilly and Company, 440 Route 22 East, Bridgewater, NJ, 08807, USA

    Hagop Youssoufian, Terry Katz & Shaila Ballal

  3. Oncology and Hematology, 3939 Houma Blvd. Suite 6, Metairie, LA, 70006–2921, USA

    Jayne Gurtler

  4. Arlington Cancer Center, 906 W. Randol Mill Road, Arlington, TX, 76012, USA

    Karel Dicke

  5. MD Anderson Cancer Center, 1400 South Orange Avenue MP 780, Orlando, FL, 32806, USA

    Omar Kayaleh

  6. University of Southern California Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Room 7310-E MC9177, Los Angeles, CA, 90033–9173, USA

    Heinz-Josef Lenz

  7. Augusta Oncology Associates PC, 1348 Walton Way Suite 4300, Augusta, GA, 30901, USA

    Mark Keaton

  8. Oncodrugs, 5 Robin Road, Warren, NJ, 07059, USA

    Eric K. Rowinsky

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  1. Andrew H. Ko
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Correspondence to Andrew H. Ko.

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Ko, A.H., Youssoufian, H., Gurtler, J. et al. A phase II randomized study of cetuximab and bevacizumab alone or in combination with gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma. Invest New Drugs 30, 1597–1606 (2012). https://doi.org/10.1007/s10637-011-9691-8

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  • DOI: https://doi.org/10.1007/s10637-011-9691-8

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