Orlando, FL—Enzalutamide did not increase the rate of seizures in men with metastatic castration-resistant prostate cancer (mCRPC) who had potential risk factors for seizure, according to results of the phase 4 UPWARD trial. The study results were reported at the 2017 Genitourinary Cancers Symposium.
“This study should provide reassurance to men taking enzalutamide. Oncologists should feel confident about prescribing enzalutamide to patients with risk factors for seizure and/or on medications to lower seizure rate,” said lead investigator Susan Slovin, MD, PhD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, New York.
“The seizure rate reported on treatment with enzalutamide in this study was comparable to that reported in men with metastatic castration-resistant prostate cancer and similar risk factors who were not exposed to enzalutamide,” she added.
Seizures were reported in 2% of patients in phase 1/2 studies of enzalutamide, but these studies used higher doses than the current standard dose of 160 mg daily. Phase 3 trials using 160 mg daily reported seizure rates of 0.3% to 0.9% with enzalutamide. The Truven Health report, a large retrospective analysis of men with mCRPC who had potential risk factors for seizure and no exposure to enzalutamide, reported a seizure incidence of 2.8 per 100 patient-years.
The global, multicenter, single-arm, open-label, postapproval UPWARD study was conducted to provide further information to regulatory bodies about the risk for seizure in enzalutamide-treated men at potentially elevated seizure risk. Of 423 men who received ≥1 doses of enzalutamide, 366 were evaluable; 100 (27%) postchemotherapy and 266 (73%) chemotherapy-naïve.
Patients enrolled in the trial had to have ≥1 potential risk factors for seizure, including history of seizure; unexplained loss of consciousness within the past 12 months; presence of brain lesions; presence of Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer; or current use of medications that may lower the seizure threshold. Patients were treated with enzalutamide 160 mg daily for 4 months.
Of the 366 evaluable patients, 4 (1.1%) had ≥1 confirmed seizures within 4 months of enzalutamide treatment initiation; 2 were treated in the chemotherapy-naïve setting and 2 in the postchemotherapy setting. For 3 of these patients, the cause of seizure events appeared to be related to enzalutamide. An additional 3 patients had a seizure possibly related to enzalutamide; all were treated in the chemotherapy-naïve setting.
Of the 7 patients with confirmed seizures, 3 continued treatment on enzalutamide, and all 3 had a second seizure. Two of these patients did not receive antiseizure medication after the first seizure.
The rate of confirmed seizure in this trial was 2.6 per 100 patient-years, which is comparable to that in the Truven Health report in men with risk factors for seizure who were not exposed to enzalutamide, Dr Slovin emphasized.
Median duration of enzalutamide treatment was 223 days as of data cut-off. Approximately 18% were treated for ≥1 years. Most other adverse events were grades 1 to 3, and were consistent with the known adverse effect profile of enzalutamide.
Dr Slovin said that enzalutamide crosses the blood–brain barrier, and that she starts fatigued patients, or those who are frail and elderly, with a lower dose so that they become acclimated to the drug.
“Depending on physical status, I might start a patient on 1 tablet per day instead of 4, and then increase the dose later,” she stated.