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

J Thorac Oncol. 2009 Aug;4(8):1002-9. doi: 10.1097/JTO.0b013e3181aba89f.


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/m2, 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 > or =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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Boronic Acids / administration & dosage
  • Bortezomib
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Pyrazines / administration & dosage
  • Quinazolines / administration & dosage
  • Salvage Therapy
  • Survival Rate
  • Treatment Outcome


  • Boronic Acids
  • Pyrazines
  • Quinazolines
  • Bortezomib
  • Erlotinib Hydrochloride