Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC.
OBJECTIVE
To evaluate the correlation between HER2 expression and gefitinib (ZD 1839, Iressa; AstraZeneca, London, United Kingdom) efficacy in terms of response rate, time to progression (TTP), and overall survival (OS) time.


METHODS
Patients with pretreated advanced non-small-cell lung cancer (NSCLC) received gefitinib at a daily dose of 250 mg until disease progression. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine HER2/epidermal growth factor receptor (EGFR) status by immunohistochemistry.


RESULTS
From February 2001 to June 2002, 63 consecutive patients were enrolled onto the study. The overall disease control rate was 58.7% (partial response [PR], 15.9%; stable disease [SD], 42.8%), median TTP was 3.3 months, and median OS was 4.1 months. Among the 43 patients in whom EGFR/HER2 status was determined, we observed six PRs (14%) and 18 SDs (42%). Disease control, including PR and SD, was 40% in the 15 patients overexpressing HER2 and 64.3% in the 28 patients not overexpressing HER2 (P =.126). No difference was found between the two groups in terms of TTP (3.5 v 3.7 months, respectively) and OS (5.7 v 6.8 months, respectively). In addition, we did not find any difference in TTP, OS, toxicity, and symptom outcome in the group of patients overexpressing both HER2 and EGFR compared with patients who had no overexpression of HER2


CONCLUSIONS
According to these data, efficacy, toxicity, and symptom outcome in patients with NSCLC treated with gefitinib do not seem to be related to HER2 expression.
Cappuzzo
Federico
F
Bellaria Hospital, Division of Medical Oncology, Via Altura 3, 40139 Bologna, Italy. federico.cappuzzo@ausl.bo.it.
Gregorc
Vanesa
V
Rossi
Elisa
E
Cancellieri
Alessandra
A
Magrini
Elisabetta
E
Paties
Carlo Terenzio
CT
Ceresoli
Giovanni
G
Lombardo
Laura
L
Bartolini
Stefania
S
Calandri
Cesare
C
de Rosa
Marisa
M
Villa
Eugenio
E
Crino
Lucio
L
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D016001:Confidence Intervals; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011300:Preoperative Care / Q000379:methods; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D000077156:Gefitinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases