First Line Gefitinib Treatment for Advanced Non-small Cell Lung Cancer (NSCLC) by the FDG-PET Metabolic Response
Gefitinib has anti-tumor activity as a result of EGFR tyrosine kinase inhibition, reducing
multiple downstream signaling processes that activate cell proliferation and other cell
responses, including cell migration angiogenesis, and reduced apoptosis. Recently, it has
been approved for the first line treatment of advanced NSCLC that harbors EGFR mutation. In
IPASS trial, tumors with EGFR mutation produced 71.2% of clinical response to first line
gefitinib while tumors with wild type EGFR showed only 1.1% of response. Therefore, patient
selection is critical for the clinical use of EGFR tyrosine kinase inhibitors as first line
When considering 1st line gefitinib treatment for NSCLC, we need EGFR mutational status of
the tumor. But most patients do not give us such information at the time of diagnosis,
because it requires tumor tissue and some time period for EGFR examination. So, we need
other strategies such as using PET scan for early prediction of response to gefitinib.
Glucose metabolic activity closely reflects responses to gefitinib therapy. In preclinical
study with gefitinib sensitive cell lines, there was a dramatic decrease in FDG uptake as
early as 2 hours after treatment. And these metabolic alterations preceded changes in cell
cycle distribution, thymidine uptake and apoptosis. In contrast, gefitinib resistant cells
exhibited no measurable changes in FDG uptake, either in cell culture or in vivo.
The strategy using FDG-PET may guide us to perform 1st line geftinib. Recently investigators
reported that FLT-PET or FDG-PET could predict response to EGFR tyrosine kinase (TKI) early
after 1 week of treatment. And % decrease more than 20% of maximum SUV of main lesion after
1 week of EGFR TKI treatment could predict response to that drug. More than 20% decrease of
SUV is a significant change during reproducibility test and also considered as a criteria
for response prediction of paclitaxel/cisplatin chemotherapy.
So, investigators develop a protocol of 1st line gefitinib treatment for NSCLC according to
FDG-PET response. And if the patient showed less than 20% decrease of peak SUV,
investigators will stop gefitinib and treat him or her with the regimen of
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective Response rate
The primary objective is to see the response rate of gefitinib in the patients who showed % decrease of peak SUV of main lesion 20% or more and continuously treated with gefitinib.
Sang-We Kim, M.D.
Asan Medical Center
South Korea: Korea Food and Drug Administration (KFDA)