Pharmacyclics, Inc's top-line results from its pivotal phase 3 clinical study of Xcytrin (motexafin gadolinium) injection, for the potential treatment of non-small cell lung cancer (NSCLC) patients with brain metastases demonstrated that although patients receiving Xcytrin had a longer time to neurologic progression, the study's primary endpoint, the difference compared to patients in the control arm did not reach statistical significance.
The randomised, controlled phase 3 trial, known as the SMART (Study of Neurologic Progression with Motexafin Gadolinium and Radiation Therapy) trial was designed to compare the safety and efficacy of whole brain radiation therapy (WBRT) alone to WBRT plus Xcytrin. The primary endpoint of the study was time to neurologic progression (TNP) as determined by a blinded events review committee. The trial enrolled 554 patients from 94 centres in North America, Europe and Australia. The treatment arms were well balanced for all known prognostic factors, claims a company release.
There was no significant difference in survival, a secondary endpoint of the trial. There were positive trends observed in favour of the Xcytrin- treated patient arm with respect to reduced steroid usage and less need for salvage radiation therapy to the brain.
Xcytrin was well tolerated in the study. The most common drug related grade 3 and 4 adverse events were hypertension (4%), elevated liver enzymes (3%) and fatigue (3%), all of which were reversible.
"While we are disappointed the trial did not meet the primary endpoint, the data do show a favourable trend in this very sick, difficult-to-treat advanced lung cancer patient population. We will complete our analysis of the data and discuss it with the FDA. We believe this study demonstrates that Xcytrin has clinical activity in lung cancer and we will continue to focus resources on its potential use in the systemic therapy of this disease," said Richard A. Miller, president and chief executive officer of Pharmacyclics.
Three trials with Xcytrin for the systemic therapy of relapsed lung cancer are in progress evaluating its use as a single agent and in combination with other agents.
Pharmacyclics is developing Xcytrin as an anti-cancer agent with a novel mechanism of action that is designed to selectively concentrate in tumours and induce apoptosis.
Xcytrin is a redox active drug that has been shown to disrupt redox dependent pathways in cells and inhibit oxidative stress related proteins. Its multifunctional mode of action provides the opportunity to be used in a broad range of cancers. Xcytrin is paramagnetic and produces an intense MRI signal, which can be used to image tumours.
Pharmacyclics is a pharmaceutical company developing innovative products to treat cancer, atherosclerosis and other diseases.