Advanced prostate cancer agent efficacious regardless of age

April 2, 2013

Older men with metastatic castration-resistant prostate cancer (CRPC) derive a similar if not superior survival benefit from treatment with enzalutamide (Xtandi) as do younger men, according to a post-hoc analysis of the phase III AFFIRM trial.

Orlando, FL-Older men with metastatic castration-resistant prostate cancer (CRPC) derive a similar if not superior survival benefit from treatment with enzalutamide (Xtandi) as do younger men, according to a post-hoc analysis of the phase III AFFIRM trial.

Relative to placebo, overall survival and progression-free survival improved equally in enzalutamide-treated men 75 years of age and older (who comprised about one-fourth of the AFFIRM study population) and men younger than 75 years of age, while tolerability was also comparable between the two groups, said first author Cora N. Sternberg, MD, at the Genitourinary Cancers Symposium in Orlando, FL.

“We know that prostate cancer, even when it’s considered castration-resistant, is still responsive to hormonal manipulation because prostate cancer remains driven by androgen receptor signaling and additionally, there are also endogenous androgens that can be activated,” she said. “Enzalutamide is an interesting drug that works specifically by blocking the androgen receptor, but also has multiple mechanisms of action which block the androgen receptor signaling pathway.”

The overall results of the AFFIRM trial demonstrated an improvement in median overall survival of 4.8 months in the patients randomized to enzalutamide versus placebo, corresponding to a 37% reduction in the risk of death. The study enrolled patients with progressive metastatic CRPC despite previous treatment with hormonal therapy and docetaxel (Taxotere) chemotherapy. Patients were randomized in a 2:1 ratio to enzalutamide, 160 mg/day, or placebo. They remained on treatment until disease progression or institution of new systemic antineoplastic treatment.

“These are patients in whom several lines of hormonal therapy, docetaxel chemotherapy, and even a second line of chemotherapy had failed,” said Dr. Sternberg, chief of medical oncology at the San Camillo & Forlanini Hospitals, Rome. “We thought it would be interesting to look at patients 75 years or older because we wanted to see if they tolerated the therapy as well as younger patients or if their outcome was worse. The study showed that they did as well or perhaps even better.”

The median duration of enzalutamide treatment was 8.2 months in the patients younger than 75 years of age versus 10.3 months in those ≥75 years of age. About 44% of the younger cohort was treated with subsequent antineoplastic therapy compared with 33% of the patients ≥75 years of age.

 

Improved survival in younger, older patients

The median overall survival in the younger men assigned to enzalutamide had not yet been reached compared with a median overall survival of 13.6 months in the younger men assigned to placebo, for a hazard ratio (HR) of 0.633 (p<.0001). In the older men, median overall survival was 18.2 months in those assigned to enzalutamide and 13.3 months in the placebo recipients, with an HR of 0.606 (p=.0044).

Radiographic progression-free survival was 8.3 months in the younger men randomized to enzalutamide compared with 2.9 months in the younger men randomized to placebo (HR=0.447; p<.0001), and 9.9 months in the older men treated with enzalutamide versus 2.8 months in the older placebo recipients (HR = 0.271; p<.0001).

The HR for time to PSA progression, compared with placebo, was 0.290 in the younger men (p<.0001) and 0.135 in the older men (p<.0001).

Fatigue was slightly more common in the older men treated with enzalutamide compared with the younger men (40% vs. 32%), and the incidence of nausea was similar between the two age cohorts (32% vs. 33%).

“The AFFIRM trial was performed in patients with metastatic CRPC after failure of docetaxel. The PREVAIL study is looking at the use of enzalutamide before chemotherapy. If the results of PREVAIL are positive, it will definitely move the field toward earlier use of hormonal therapy-pre-chemotherapy,” said Dr. Sternberg.

Dr. Sternberg has received honoraria from Astellas Pharma. Several of her co-authors have received honoraria or research funding from or have other interests in Astellas Pharma and/or Medivation.UT