I was attending the 2010 ASCO Annual Meeting this past weekend, June 5-6, and will post some blogs about my "highlights." This is a perk of living in Chicago since the meetings were here from 2006-2008 and will be here for the next ten meetings!
Dr. Joan H. Schiller, from the University of Texas Southwestern Medical Center, presented the findings of the the ARQ 197-209 Clinical Trial Group during Saturday’s Clinical Science Symposium on “Molecularly Targeted Trials in Lung Cancer” (Abstract LBA7502). ARQ 197-209 is an investigational agent that is an inhibitor of c-MET, a high-affinity tyrosine kinase receptor for hepatocyte growth factor. The c-MET receptor is an attractive anticancer target in NSCLC given that c-MET gene amplification correlates with a poor prognosis in NSCLC and is also a mechanism for resistance to EGFR inhibitors such as erlotinib.
This was a phase II, randomized, double-blind, placebo-controlled trial that studied 167 patients with locally advanced or metastatic NSCLC who were randomly assigned 1:1 to treatment with erlotinib plus either ARQ 197 or placebo. The primary objective of the study was to compare PFS between the two arms. Although study participants had received at least one prior chemotherapy regimen, all were required to be naïve to EGFR inhibitors for study inclusion.
Results. The addition of ARQ 197 to erlotinib significantly prolonged PFS by a median of 6.4 weeks after adjustment for key prognostic factors in the Cox regression model (p < 0.05).
An additional interesting finding was that the benefits of adding ARQ 197 to erlotinib were more marked when analyses were restricted to the 111 patients with non-squamous cell histology. Patients in this subgroup who received ARQ 197/erlotinib as compared with erlotinib alone demonstrated a significant 9.2-week improvement in PFS (adjusted HR = 0.61; p < 0.05), as well as a significant 13.7-week improvement in OS (adjusted HR = 0.58; p < 0.05).
Another provocative finding was found in their exploratory analyses based on NSCLC molecular features which suggest that ARQ 197 also yields particularly prominent PFS improvements in KRAS mutant disease, most commonly found in smokers, and perhaps EGFR wild-type disease as well.