Phase II Study Of STI571 (Gleevec^TM) For Patients With Small Cell Lung Cancer

Reviewer: Roberto Santiago, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 21, 2002

Presenter: Bruce E Johnson
Presenter's Affiliation: Dana-Farber Cancer Inst, Boston, MA
Type of Session: Scientific

Background

STI571 is a small molecule that inhibits the tyrosine kinase activity of the BCR-Abl and Kit receptors
The oral preparation of STI571 has been proven safe and very efficacious against CML (BCR-ABL positive) and GIST (Kit positive)
The activation of the Kit receptor by the ligand ?stem cell factor? (SCF) has been implicated in the establishment of an autocrine growth loop in small cell lung cancer (SCLC)
Published literature has suggested that Kit is expressed on 50-70% of SCLC cells

Materials and Methods

Phase II trial designed to evaluate STI571 in patients with SCLC who were either chemotherapy naïve (CN) or had maintained a response for ≥ 60 days to a previous treatment (sensitive relapse, SR)
Enrollment of CN patients was limited to patients with extensive stage SCLC
The primary end point was objective response rate (OR) to STI571 (600 mg/day)
Between 11/006 and 4/01, 16 men and 3 women with histologically-confirmed SCLC were enrolled on the trial; 9 were CN with extensive stage SCLC and 10 were in SR
ECOG performance status ranged from 0-2 (0, 42%; 1, 47%; and 2, 11%)
The median age was 58 (range 39-74)

Results

No grade 4 tocixity was observed
One case of grade 3 vomiting and one case of grade 3 CNS toxicity (seizure) were observed
No OR were observed
The median time to tumor progression was 24 days (range 18-52 days) in the CN patients
The median time to tumor progression was 42 days (range 7-126 days) in the SR patients
One patient had stable disease for 90 days
Immunohistochemical staining for Kit was performed in 14 tumor blocks
Only 28% (4/14) stained positive for Kit
The time to tumor progression for the 2 CN patients with tumors positive for Kit were 37 and 52 days
The time to tumor progression for the 2 SR patients with tumors positive for Kit were 35 and 68 days
The 6-months overall survival was 68%

Author's Conclusions

STI571 was well tolerated in SCLC patients
The study is limited by the small number of patients, particularly Kit positive patients
Immunohistochemical tests for Kit yielded a lower rate of Kit positivity than that described on the literature for SCLC cells
The objective response to STI571 in these SCLC patients was disappointedly low

Clinical/Scientific Implications

Any conclusions from this study should take into account the small number of Kit positive SCLC patients actually treated
Some of the studies suggesting higher rates of Kit expression on SCLC cells have used other techniques for detection such as FISH
Further testing of STI571 as a single agent will focus on confirmation of SCLC histology and the demonstration of Kit expression

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.