TY - JOUR
T1 - Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/phospho-akt-positive or never smoker patients with advanced non-small-cell lung cancer
T2 - The ONCOBELL trial
AU - Cappuzzo, Federico
AU - Ligorio, Claudia
AU - Jänne, Pasi A.
AU - Toschi, Luca
AU - Rossi, Elisa
AU - Trisolini, Rocco
AU - Paioli, Daniela
AU - Holmes, Alison J.
AU - Magrini, Elisabetta
AU - Finocchiaro, Giovanna
AU - Bartolini, Stefania
AU - Cancellieri, Alessandra
AU - Ciardiello, Fortunato
AU - Patelli, Marco
AU - Crino, Lucio
AU - Varella-Garcia, Marileila
PY - 2007/6/1
Y1 - 2007/6/1
N2 - Purpose: In non-small-cell lung cancer (NSCLC), clinical and biologic predictors for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitivity have been identified in retrospective studies, and there is urgent need to validate these results in prospective trials. The ONCOBELL trial is a prospective phase II study evaluating gefitinib sensitivity in NSCLC patients who never smoked or have increased EGFR gene copy number or activation of the antiapoptotic protein Akt. Patients and Methods: EGFR gene copy number was evaluated using fluorescence in situ hybridization (FISH), and presence of phospho-Akt was evaluated using immunohistochemistry. Additional tests included immunohistochemistry analysis of EGFR, FISH analysis of HER2, and mutation analysis of EGFR, HER2, and K-ras. Results: From November 2004 to February 2006, 183 patients were screened, and 42 patients were enrolled onto the trial. We observed one complete and 19 partial responses, for an overall response rate (RR) of 47.6% (95% CI, 32.5% to 62.7%). Median duration of response was 6.1 months, median time to progression (TTP) was 6.4 months, 1-year survival rate was 64.3%, and median survival time was not reached. EGFR FISH-positive patients, compared with negative patients, had higher RR (68.0% v 9.1%, respectively; P <.001), longer TTP (7.6 v 2.7 months, respectively; P = .02), and a trend for longer survival (median survival not reached v 7.4 months, respectively; P = .3). Therapy was well tolerated, and there were no drug-related deaths. Median follow-up time was too short for significance tests of differences in survival outcomes. Conclusion: Gefitinib is active and well tolerated in patients with trial characteristics, and EGFR FISH analysis is an accurate predictor for such therapy.
AB - Purpose: In non-small-cell lung cancer (NSCLC), clinical and biologic predictors for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitivity have been identified in retrospective studies, and there is urgent need to validate these results in prospective trials. The ONCOBELL trial is a prospective phase II study evaluating gefitinib sensitivity in NSCLC patients who never smoked or have increased EGFR gene copy number or activation of the antiapoptotic protein Akt. Patients and Methods: EGFR gene copy number was evaluated using fluorescence in situ hybridization (FISH), and presence of phospho-Akt was evaluated using immunohistochemistry. Additional tests included immunohistochemistry analysis of EGFR, FISH analysis of HER2, and mutation analysis of EGFR, HER2, and K-ras. Results: From November 2004 to February 2006, 183 patients were screened, and 42 patients were enrolled onto the trial. We observed one complete and 19 partial responses, for an overall response rate (RR) of 47.6% (95% CI, 32.5% to 62.7%). Median duration of response was 6.1 months, median time to progression (TTP) was 6.4 months, 1-year survival rate was 64.3%, and median survival time was not reached. EGFR FISH-positive patients, compared with negative patients, had higher RR (68.0% v 9.1%, respectively; P <.001), longer TTP (7.6 v 2.7 months, respectively; P = .02), and a trend for longer survival (median survival not reached v 7.4 months, respectively; P = .3). Therapy was well tolerated, and there were no drug-related deaths. Median follow-up time was too short for significance tests of differences in survival outcomes. Conclusion: Gefitinib is active and well tolerated in patients with trial characteristics, and EGFR FISH analysis is an accurate predictor for such therapy.
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U2 - 10.1200/JCO.2006.09.4300
DO - 10.1200/JCO.2006.09.4300
M3 - Article
C2 - 17538169
AN - SCOPUS:34250161814
VL - 25
SP - 2248
EP - 2255
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 16
ER -