TY - JOUR
T1 - A randomized phase 2 study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer
AU - Lynch, Thomas J.
AU - Fenton, David
AU - Hirsh, Vera
AU - Bodkin, David
AU - Middleman, Edward L.
AU - Chiappori, Alberto
AU - Halmos, Balazs
AU - Favis, Reyna
AU - Liu, Hua
AU - Trepicchio, William L.
AU - Eton, Omar
AU - Shepherd, Frances A.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Advanced non-small cell lung cancer
KW - Bortezomib
KW - Erlotinib
KW - Phase 2
UR - http://www.scopus.com/inward/record.url?scp=68349122406&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68349122406&partnerID=8YFLogxK
U2 - 10.1097/JTO.0b013e3181aba89f
DO - 10.1097/JTO.0b013e3181aba89f
M3 - Article
C2 - 19633475
AN - SCOPUS:68349122406
SN - 1556-0864
VL - 4
SP - 1002
EP - 1009
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 8
ER -