A randomized phase 2 study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer

Thomas J. Lynch, David Fenton, Vera Hirsh, David Bodkin, Edward L. Middleman, Alberto Chiappori, Balazs Halmos, Reyna Favis, Hua Liu, William L. Trepicchio, Omar Eton, Frances A. Shepherd

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48 Scopus citations


INTRODUCTION: This phase 2 study was conducted to determine the efficacy and safety of erlotinib alone and with bortezomib in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with histologically or cytologically confirmed relapsed or refractory stage IIIb/IV NSCLC were randomized (1:1; stratified by baseline histology, smoking history, sex) to receive erlotinib 150 mg/d alone (arm A; n = 25) or in combination with bortezomib 1.6 mg/m, days 1 and 8 (arm B; n = 25) in 21-day cycles. Responses were assessed using Response Evaluation Criteria in Solid Tumors. Tumor samples were evaluated for mutations predicting response. Six additional patients received the combination in a prior dose deescalation stage and were included in safety analyses. RESULTS: Response rates were 16% in arm A and 9% in arm B; disease control rates were 52 and 45%, respectively. The study was halted at the planned interim analysis due to insufficient clinical activity in arm B. Median progression-free survival and overall survival were 2.7 and 7.3 months in arm A, and 1.3 and 8.5 months in arm B. Six-month survival rates were 56.0% in both arms; 12-month rates were 40 and 30% in arms A and B, respectively. Response rate to erlotinib±bortezomib was significantly higher in patients with epidermal growth factor receptor mutations (50 versus 9% for wild type). The most common treatment-related grade ≥3 adverse event was skin rash (three patients in each treatment group). CONCLUSION: Insufficient activity was seen with erlotinib plus bortezomib in patients with relapsed/refractory advanced NSCLC to warrant a phase 3 study of the combination.

Original languageEnglish (US)
Pages (from-to)1002-1009
Number of pages8
JournalJournal of Thoracic Oncology
Issue number8
StatePublished - Aug 2009



  • Advanced non-small cell lung cancer
  • Bortezomib
  • Erlotinib
  • Phase 2

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Lynch, T. J., Fenton, D., Hirsh, V., Bodkin, D., Middleman, E. L., Chiappori, A., Halmos, B., Favis, R., Liu, H., Trepicchio, W. L., Eton, O., & Shepherd, F. A. (2009). A randomized phase 2 study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer. Journal of Thoracic Oncology, 4(8), 1002-1009. https://doi.org/10.1097/JTO.0b013e3181aba89f