Gefitinib or Docetaxel as Second Line Therapy for Wild-type Epidermal Growth Factor Receptor (EGFR) NSCLC
Status:
Unknown status
Trial end date:
2014-12-01
Target enrollment:
Participant gender:
Summary
Gefitinib, the first EGFR-tyrosine kinase inhibitor (TKI) in the world was examined as
monotherapy in two phase Ⅱ studies called IDEAL trials. Response rate with doses of 250mg and
500mg/day were similar, ranging from 10% to 18%. Posterior analysis demonstrated that
patients with EGFR mutation had an improved response rate (RR) to gefitinib compared to
wild-type patients (46% versus 10%). The early trials that evaluated EGFR-TKIs for the
second- and third-line settings of advanced NSCLC did not select patients on the basis of any
EGFR marker. The IEESSA Survival Evaluation in Lung Cancer (ISEL) trial evaluated the role of
second-line gefitinib 250mg/day in 1692 patients with advanced NSCLC. Patients with EGFR
mutations had higher RR than patients without (37.5% versus 2.6%). From the above results,
the response rate in patients without EGFR gene mutation was obviously different (10% versus
2.6%). The methods used for detecting EGFR gene mutation was different, which might
contribute to the difference of response rates. In IDEAL trial, EGFR gene mutation was
detected by sequencing. But in ISEL trial, EGFR gene mutation was detected by ARMS. As we
know, ARMS was more sensitive than sequencing in detecting EGFR gene mutation. That is to
say, in IDEAL trials some EGFR mutant patients were misdiagnosed as wild-type patients, so
the response rate was higher. Recently, Wu Yi-Long et al reported that relative abundance of
EGFR mutations predicted benefit form gefitinib treatment for advanced non small cell lung
cancer. The study cohort was all Chinese. In this study, the objective response rate in
patients without EGFR mutation detected by ARMS was 16.1%, which was significantly higher
than the response rate of docetaxel. But in 2012 American society of clinical oncology (ASCO)
annual meeting, the Tailor study in which Italian NSCLC patients were enrolled demonstrated a
clear superiority of docetaxel over erlotinib as second line treatment for patients without
EGFR mutations in exons 19 or 21. So we wonder if the racial difference is the determinant
factor. So the purpose of this trial is to compare the efficacy and safety of gefitinib with
docetaxel as second-line therapy for advanced or metastatic Chinese NSCLC patients with
wild-type EGFR.