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A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma

  • PHASE II STUDIES
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Summary

Background There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. Methods A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. Results Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1–18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.

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Acknowledgments

This trial is supported by the NCI. N01-CM-2011-00099 (P2C), N01-CM-2011-00032 (PMH), N01-CM-2011-00100 (Moffitt), N01-CM-2011-00038 (California), N01-CM-2011-00070 (OSU) contracts

Potential conflict of interest

Dr Strosberg: Genentech and Pfizer, limited honoraria.

Dr Saab: Genentech, paid consultant

Dr Knox: Pfizer, research support.

Author information

Authors and Affiliations

  1. Staff Medical Oncologist, Gastrointestinal Oncology Lead, Princess Margaret Cancer Centre, University of Toronto, 5-210, 610 University Ave, Toronto, ON, M5G 2 M9, USA

    Jennifer J. Knox

  2. Mayo Clinic, Rochester, MN, USA

    Rui Qin & Charles Erlichman

  3. H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

    Jonathan R. Strosberg

  4. Washington University School of Medicine, St Louis, MO, USA

    Benjamin Tan

  5. Montefiore Medical Center, Bronx, NY, USA

    Andreas Kaubisch

  6. University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA

    Anthony B. El-Khoueiry

  7. The Wexner Medical Center at the Ohio State University, Columbus, OH, USA

    Tanios S. Bekaii-Saab

  8. Metro Minnesota CCOP, St Louis Park, MN, USA

    Steven R. Rousey

  9. National Cancer Institute, Bethesda, MD, USA

    Helen X. Chen

Authors
  1. Jennifer J. Knox
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  2. Rui Qin
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  3. Jonathan R. Strosberg
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  4. Benjamin Tan
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  5. Andreas Kaubisch
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  6. Anthony B. El-Khoueiry
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  7. Tanios S. Bekaii-Saab
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  8. Steven R. Rousey
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  9. Helen X. Chen
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  10. Charles Erlichman
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Corresponding author

Correspondence to Jennifer J. Knox.

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Knox, J.J., Qin, R., Strosberg, J.R. et al. A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma. Invest New Drugs 33, 241–246 (2015). https://doi.org/10.1007/s10637-014-0169-3

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  • DOI: https://doi.org/10.1007/s10637-014-0169-3

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