FDA Approves Enzalutamide for Prostate Cancer

Enzalutamide – an oral agent formerly known as MDV3100 – has won Food and Drug Administration approval as a second-line treatment for metastatic castration-resistant prostate cancer.

The new agent, to be marketed under the brand name Xtandi, is the latest in a stream of new therapies transforming treatment of prostate cancer. Other approvals within the last 3 years include the cancer vaccine sipuleucel-T (Provenge), abiraterone (Zytiga), cabazitaxel (Jevtana), and denosumab (Prolia, Xgeva) for bone-related indications.

Only the timing of the enzalutamide decision, announced Aug. 31 at the start of the Labor Day weekend, was a surprise. It came 3 months earlier than the Nov. 22 deadline set for FDA action under the agency’s priority review program.

"The need for additional treatment options for advanced prostate cancer continues to be important for patients. Xtandi is the latest treatment for this disease to demonstrate its ability to extend a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Enzalutamide inhibits signaling by the androgen receptor. Approval is based on results of the randomized, double-blind, placebo-controlled AFFIRM trial, the results of which were published Aug. 15 online (N. Engl. J. Med. 2012 [doi: 10.1056/NEJMoa1207506]).

The new agent prolonged overall survival by a median of 4.8 months and reduced the risk of death by 37% in the study, which evaluated 1,199 patients with metastatic castration-resistant prostate cancer who had received prior treatment with docetaxel (Taxotere). Medium overall survival reached 18.4 months with enzalutamide vs. 13.6 months with placebo.

The FDA noted that about 1% of patients receiving enzalutamide had seizures and stopped therapy. The study had excluded patients with "a history of seizure, an underlying brain injury with loss of consciousness, a temporary decrease in blood to the brain within the past 12 months, a stroke, brain metastases, an abnormal connection of the arteries and veins in the brain, or patients taking medications that may lower the seizure threshold."

The announcement advised, "The safety of Xtandi is unknown in patients with these conditions."

Otherwise, the most common side effects listed by the FDA were "weakness or fatigue, back pain, diarrhea, joint pain, hot flush, tissue swelling, musculoskeletal pain, headache, upper respiratory infections, dizziness, spinal cord compression and cauda equina syndrome, muscular weakness, difficulty sleeping, lower respiratory infections, blood in urine, tingling sensation, anxiety, and high blood pressure."

Enzalutamide will be co-marketed by Astellas Pharma U.S., Inc. of Northbrook, Ill., and Medivation Inc. of San Francisco.

Enzalutamide – an oral agent formerly known as MDV3100 – has won Food and Drug Administration approval as a second-line treatment for metastatic castration-resistant prostate cancer.

The new agent, to be marketed under the brand name Xtandi, is the latest in a stream of new therapies transforming treatment of prostate cancer. Other approvals within the last 3 years include the cancer vaccine sipuleucel-T (Provenge), abiraterone (Zytiga), cabazitaxel (Jevtana), and denosumab (Prolia, Xgeva) for bone-related indications.

Only the timing of the enzalutamide decision, announced Aug. 31 at the start of the Labor Day weekend, was a surprise. It came 3 months earlier than the Nov. 22 deadline set for FDA action under the agency’s priority review program.

"The need for additional treatment options for advanced prostate cancer continues to be important for patients. Xtandi is the latest treatment for this disease to demonstrate its ability to extend a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Enzalutamide inhibits signaling by the androgen receptor. Approval is based on results of the randomized, double-blind, placebo-controlled AFFIRM trial, the results of which were published Aug. 15 online (N. Engl. J. Med. 2012 [doi: 10.1056/NEJMoa1207506]).

The new agent prolonged overall survival by a median of 4.8 months and reduced the risk of death by 37% in the study, which evaluated 1,199 patients with metastatic castration-resistant prostate cancer who had received prior treatment with docetaxel (Taxotere). Medium overall survival reached 18.4 months with enzalutamide vs. 13.6 months with placebo.

The FDA noted that about 1% of patients receiving enzalutamide had seizures and stopped therapy. The study had excluded patients with "a history of seizure, an underlying brain injury with loss of consciousness, a temporary decrease in blood to the brain within the past 12 months, a stroke, brain metastases, an abnormal connection of the arteries and veins in the brain, or patients taking medications that may lower the seizure threshold."

The announcement advised, "The safety of Xtandi is unknown in patients with these conditions."

Otherwise, the most common side effects listed by the FDA were "weakness or fatigue, back pain, diarrhea, joint pain, hot flush, tissue swelling, musculoskeletal pain, headache, upper respiratory infections, dizziness, spinal cord compression and cauda equina syndrome, muscular weakness, difficulty sleeping, lower respiratory infections, blood in urine, tingling sensation, anxiety, and high blood pressure."

Enzalutamide will be co-marketed by Astellas Pharma U.S., Inc. of Northbrook, Ill., and Medivation Inc. of San Francisco.

Enzalutamide – an oral agent formerly known as MDV3100 – has won Food and Drug Administration approval as a second-line treatment for metastatic castration-resistant prostate cancer.

The new agent, to be marketed under the brand name Xtandi, is the latest in a stream of new therapies transforming treatment of prostate cancer. Other approvals within the last 3 years include the cancer vaccine sipuleucel-T (Provenge), abiraterone (Zytiga), cabazitaxel (Jevtana), and denosumab (Prolia, Xgeva) for bone-related indications.

Only the timing of the enzalutamide decision, announced Aug. 31 at the start of the Labor Day weekend, was a surprise. It came 3 months earlier than the Nov. 22 deadline set for FDA action under the agency’s priority review program.

"The need for additional treatment options for advanced prostate cancer continues to be important for patients. Xtandi is the latest treatment for this disease to demonstrate its ability to extend a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Enzalutamide inhibits signaling by the androgen receptor. Approval is based on results of the randomized, double-blind, placebo-controlled AFFIRM trial, the results of which were published Aug. 15 online (N. Engl. J. Med. 2012 [doi: 10.1056/NEJMoa1207506]).

The new agent prolonged overall survival by a median of 4.8 months and reduced the risk of death by 37% in the study, which evaluated 1,199 patients with metastatic castration-resistant prostate cancer who had received prior treatment with docetaxel (Taxotere). Medium overall survival reached 18.4 months with enzalutamide vs. 13.6 months with placebo.

The FDA noted that about 1% of patients receiving enzalutamide had seizures and stopped therapy. The study had excluded patients with "a history of seizure, an underlying brain injury with loss of consciousness, a temporary decrease in blood to the brain within the past 12 months, a stroke, brain metastases, an abnormal connection of the arteries and veins in the brain, or patients taking medications that may lower the seizure threshold."

The announcement advised, "The safety of Xtandi is unknown in patients with these conditions."

Otherwise, the most common side effects listed by the FDA were "weakness or fatigue, back pain, diarrhea, joint pain, hot flush, tissue swelling, musculoskeletal pain, headache, upper respiratory infections, dizziness, spinal cord compression and cauda equina syndrome, muscular weakness, difficulty sleeping, lower respiratory infections, blood in urine, tingling sensation, anxiety, and high blood pressure."

Enzalutamide will be co-marketed by Astellas Pharma U.S., Inc. of Northbrook, Ill., and Medivation Inc. of San Francisco.