ATLANTA—Motexafin gadolinium (MGd, Xcytrin) combined with whole brain radiation therapy (WBRT) prolongs time to neurologic progression in non-small-cell lung cancer (NSCLC) patients with brain metastases if treatment starts within 3 weeks of the brain metastasis diagnosis, according to data from a phase III trial. Minesh P. Mehta, MD, presented the results at the American Society of Clinical Oncology 42nd Annual Meeting (abstract 7014).
All patients in the study, known as SMART (Study of Neurologic Progression With Motexafin Gadolinium and Radiation Therapy), had NSCLC with brain metastases. Patients were randomized to receive WBRT 30 Gy in 10 fractions or WBRT plus MGd 5 mg/kg/d for 10 days.
Patients were seen monthly for 8 months, then every 2 months, for standardized neurologic examination and treatstandardized neurocognitive testing using a battery of validated tests assessing memory, verbal fluency, and executive function.
The time to neurologic progression endpoint measured major decline in neurologic function, based on prespecified events such as change in level of consciousness, aphasia/dysphasia/dysarthria, hemiparesis, new visual field defects, ataxia, cranial nerve palsy, and neurocognitive progression in all domains.
Patients were enrolled from centers in North America, Europe, and Australia. Most patients (81%) had multiple brain metastases; 51% had extracranial metastases, and 84% presented with neurologic deficits.
Overall, mean time from brain metastases diagnosis to randomization for the MGd arm was 4.3 weeks vs 3.3 weeks for controls, an imbalance that adversely affected outcomes in the MGd arm.
Time to Progression
Dr. Mehta reported that median time to progression (as measured from randomization) in the intent-to-treat population of 554 patients was 15.37 months in the MGd group vs 10.03 months in the WBRT-alone group (HR 0.78, P = .12). Analyses correcting for the imbalance in treatment delay between the two arms (by measuring from time of brain metastasis diagnosis) showed that median time to neurologic progression was 15.53 months for those receiving MGd/WBRT vs 10.2 months for controls (HR 0.75, P = .05).