A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma

Julie E. Bauman, Hugo Arias-Pulido, Sang Joon Lee, M. Houman Fekrazad, Hiroyuki Ozawa, Elana Fertig, Jason Howard, Justin Bishop, Hao Wang, Garth T. Olson, Michael J. Spafford, Dennie V. Jones, Christine H. Chung

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Objectives: The epidermal growth factor receptor (EGFR) is a validated target in head and neck squamous cell carcinoma (HNSCC). In recurrent and/or metastatic (R/M) HNSCC, resistance to anti-EGFR therapy inevitably occurs. Downstream activation of the PI3K/Akt/mTOR pathway is an established resistance mechanism. Concurrent mTOR blockade may improve efficacy of anti-EGFR therapy. Materials and methods: Erlotinib 150 mg daily and temsirolimus 15 mg weekly were administered to patients with platinum-refractory R/M HNSCC and ECOG performance status 0-2. The primary endpoint was progression-free survival (PFS). Correlative studies determined PIK3CA and HRAS mutation status; p16, EGFR, pS6K, pAkt and PTEN expression; and pre- and post-treatment plasma levels of 20 immunomodulatory cytokines. Results: Twelve patients enrolled; six withdrew within 6 weeks due to toxicity or death, prompting early closure of the trial. Grade ≥ 3 toxicities included fatigue, diarrhea, gastrostomy tube infection, peritonitis, pneumonia, dyspnea, and HN edema. Median PFS was 1.9 months. Median overall survival was 4.0 months. Six/12 tumors were p16(+), 9/11 lacked measurable PTEN expression, and 1/12 harbored a PIK3CA mutation. On exploratory analysis, high baseline plasma VEGF and interferon-gamma levels marginally associated with tumor progression. Conclusions: The combination of erlotinib and temsirolimus was poorly tolerated. Low prevalence of PTEN expression and 8% incidence of PIK3CA mutations indicate biological relevance of this pathway in R/M disease. Investigation of more tolerable combinations of EGFR and PI3K/Akt/mTOR pathway inhibitors in selected HNSCC patients is warranted.

Original languageEnglish (US)
Pages (from-to)461-467
Number of pages7
JournalOral Oncology
Volume49
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • EGFR
  • Erlotinib
  • Head and neck squamous cell carcinoma
  • PIK3CA
  • Platinum-refractory
  • Temsirolimus
  • mTOR

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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  • Cite this

    Bauman, J. E., Arias-Pulido, H., Lee, S. J., Fekrazad, M. H., Ozawa, H., Fertig, E., Howard, J., Bishop, J., Wang, H., Olson, G. T., Spafford, M. J., Jones, D. V., & Chung, C. H. (2013). A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma. Oral Oncology, 49(5), 461-467. https://doi.org/10.1016/j.oraloncology.2012.12.016