GEFITINIB-ERLOTINIB MAY SLOW CNS METASTASES IN NSCLC

NEW YORK (Reuters Health) Nov 09 - The tyrosine kinase inhibitors gefitinib or erlotinib may slow the development of central nervous system metastases in patients with advanced non-small cell lung cancer (NSCLC), if they carry sensitizing EGFR mutations.

Those findings come from a Boston-based team, reporting in the October 28 online issue of Clinical Cancer Research. "The study showed the risk of developing brain metastases and/or progression of pre-existing brain lesions in patients with EGFR mutations treated with the targeted agents, erlotinib or gefitinib, was approximately one-half the published rate of other patients with NSCLC given chemotherapy," lead author Dr. Stephanie Heon commented via email.

Dr. Heon along with Dr. Bruce E. Johnson at the Dana-Farber Cancer Institute, and other colleagues note that CNS involvement is a frequent occurrence in patients with NSCLC. Gefitinib and erlotinib can penetrate into the CNS, but their impact on the development and control of CNS metastases is unclear.

"The prevention and control of brain metastases is emerging as a more vital component of overall disease control and quality of life in patients with lung cancer," Dr. Heon pointed out, "because the systemic therapies for patients with lung cancer continue to improve, particularly within genetically defined subsets given targeted agents."

Reviewing their 6-year experience with routine EGFR characterization in lung cancer patients, the researchers identified 100 patients with stage IIIB/IV NSCLC and somatic EGFR mutations treated with gefitinib or erlotinib.

"Eighty-four patients have progressed after a median potential follow-up of 42.2 months," the team reports. "The median overall survival for the entire cohort was 33.1 months."

The median time to progression was 13.1 months, and 28 patients developed CNS progression -- 8 of whom had previously treated brain metastases, according to the report.

Dr. Heon and colleagues calculate that the actuarial risks of CNS progression at 1 year and 2 years were 7% and 19% respectively. That compares with historical rates of CNS failure of 40-55% following definitive therapy of stage III NSCLC.

"We are now in the process of evaluating whether the lower frequency of CNS metastases in these patients is caused by a different underlying biological behavior of these tumors, or whether the lower frequency is likely caused by the treatment with gefitinib or erlotinib," Dr. Heon explained.

She said the ability of gefitinib or erlotinib to delay or prevent the appearance of CNS disease in patients with dramatic systemic responses is a major step forward in managing patients with EGFR mutations.

Meanwhile, she and her coauthors conclude, "Further research is needed to distinguish between the underlying rates of developing CNS metastases between NSCLC with and without EGFR mutations and the impact of gefitinib and erlotinib versus chemotherapy on CNS failure patterns in these patients."

Clin Cancer Res. Posted online October 28, 2010. Abstract