Erlotinib for frontline treatment of advanced non-small cell lung cancer: a phase II study.
OBJECTIVE
Erlotinib has proven activity in pretreated patients with advanced non-small cell lung cancer (NSCLC). We evaluated erlotinib in the frontline treatment of advanced NSCLC and assessed biological predictors of outcome.


METHODS
In this phase II study, chemotherapy-naive patients with stage IIIB/IV NSCLC received oral erlotinib (150 mg/d) until disease progression or unacceptable toxicity occurred. Tumor response was assessed every 6 weeks, and samples were analyzed for potential molecular markers of treatment response and survival. The primary end point was the proportion of patients without disease progression after 6 weeks of treatment.


RESULTS
Fifty-three patients were eligible. The overall rate of nonprogression at 6 weeks was 52.8% (28 of 53 patients). Tumor response rate was 22.7%, with 1 complete response, 11 partial responses, and 16 cases of stable disease. Responses were seen across most patient clinical characteristics. The median duration of tumor response was 333 days; median overall survival was 391 days; and median time to disease progression was 84 days. Erlotinib was well tolerated, the main treatment-related adverse events being mild-to-moderate rash and diarrhea. Histologic material for biological studies was available in 29 cases. Four of five responders and one patient with stable disease had a classic epidermal growth factor receptor tyrosine kinase mutation. Two progressing patients exhibited epidermal growth factor receptor point mutations (one with T790M mutation), and K-ras mutations were detected in 10 nonresponders.


CONCLUSIONS
Erlotinib shows significant antitumor activity in the first-line treatment of advanced NSCLC and may be a viable alternative to chemotherapy. Patient selection cannot easily be based on clinical or biological variables.
Giaccone
Giuseppe
G
Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam, the Netherlands. g.giaccone@vumc.nl
Gallegos Ruiz
Marielle
M
Le Chevalier
Thierry
T
Thatcher
Nick
N
Smit
Egbert
E
Rodriguez
Jose Antonio
JA
Janne
Pasi
P
Oulid-Aissa
Dalila
D
Soria
Jean-Charles
JC
D000284:Administration, Oral; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D017931:DNA Primers; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D011905:Genes, ras; D006801:Humans; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D011799:Quinazolines / Q000627:therapeutic use* / Q000633:toxicity; D013607:Tablets
D000970:Antineoplastic Agents; D017931:DNA Primers; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013607:Tablets; D000069347:Erlotinib Hydrochloride; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D066246:ErbB Receptors