Men with advanced prostate cancer treated with investigational enzalutamide (formerly MDV3100) demonstrated a significantly higher response rate in health-related quality of life compared with placebo, according to new data from the phase 3 AFFIRM study.
Men with advanced prostate cancer treated with investigational enzalutamide (formerly MDV3100) demonstrated a significantly higher response rate in health-related quality of life (QOL) compared with placebo, according to new data from the phase 3 AFFIRM study.
The findings were presented at the 2012 American Society of Clinical Oncology Annual Meeting in Chicago, Ill., (abstract #4519) by Johann de Bono, MBChB, FRCP, MSc, PhD, of The Institute of Cancer Research and Royal Marsden Hospital, London, and co-principal investigator of the AFFIRM trial.
The phase 3 AFFIRM trial was a randomized, double-blind, placebo-controlled, multinational trial evaluating enzalutamide (160 mg/day) versus placebo in 1,199 men with advanced prostate cancer who were previously treated with docetaxel-based chemotherapy but had stopped responding. The primary end point was overall survival, with secondary end points including radiographic progression-free survival, time to first skeletal-related event, time to prostate-specific antigen (PSA) progression, and circulating tumor cell count conversion rate.
According to a joint statement from Medivation and Astellas Pharma, the companies that sponsored the study, patients responded to the Functional Assessment of Cancer Therapy – Prostate (FACT-P) questionnaire, a validated instrument comprising 27 core items to assess factors like level of energy, ability to cope with illness, level of pain, ability to work, and amount of support from family/friends. The researchers noted that 43.2% of men taking enzalutamide had an improvement in QOL versus 18.3% who took placebo. The improved response was based on a 10-point or greater increase in a patient’s overall score.
Additionally, men taking enzalutamide saw a delayed occurrence of first skeletal-related events (16.7 months), defined as a pathologic bone fracture, change of anti-cancer therapy to treat bone pain, spinal cord compression, or surgery or radiation therapy to bone, compared with those who took placebo (13.6 months, P=.0001, HR=0.688).
Data presented earlier this year showed that the drug reduced the risk of death by 37% compared with placebo, prompting the Independent Data Monitoring Committee to recommend unblinding the study to offer enzalutamide to all participants. Patients on the drug had a median overall survival of 18.4 months versus 13.6 months for those on placebo.
“The success of this trial could give doctors a new therapy option for men with advanced prostate cancer,” noted Bono in the press release.
Enzalutamide inhibits the activity of prostate cancer androgen receptors by inhibiting testosterone binding to androgen receptors, nuclear translocation of androgen receptors, and DNA binding and activation by androgen receptors; thus reducing the serum PSA level.
Common side effects observed more frequently in patients treated with enzalutamide compared with placebo included fatigue, diarrhea, and hot flush. However, serious adverse events were lower among patients treated with enzalutamide than those in the placebo group. Seizure was reported in <1% of patients treated with enzalutamide.
Medivation and Astellas Pharma announced May 21 they had submitted a New Drug Application to FDA for enzalutamide, and they have requested priority review.