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The results of the double-blind, phase III trial were presented at the 2019 ASCO Genitourinary Cancers Symposium.
Men with metastatic hormone-sensitive prostate cancer who received enzalutamide in addition to androgen deprivation therapy (ADT) had higher response rates than those who received ADT plus placebo, according to the results of the double-blind, phase III ARCHES trial presented at the 2019 ASCO Genitourinary Cancers Symposium.
The study included 1,150 men with metastatic hormone-sensitive prostate cancer who were randomized to receive either ADT with enzalutamide (n = 574) or ADT with placebo (n = 576). Patients were stratified by volume of disease (low vs high) and receipt of prior docetaxel.
Patients had a median age of 70 years and were from Europe, North America, and the Asia-Pacific region. About two-thirds of patients in each arm had high disease volume, and 18% of patients in each arm received prior treatment with docetaxel. About two-thirds of patients had distant metastasis at initial diagnosis, and about two-thirds had a Gleason score of at least 8.
The trial met its primary endpoint, showing that, at a median follow-up of 14.4 months, patients on the enzalutamide arm had prolonged radiographic progression-free survival (rPFS) compared with those on the placebo arm, and a 61% improvement in the risk of progression or death over time (hazard ratio [HR], 0.39; 95% CI, 0.30–0.50; P < .0001). A higher portion of patients on the enzalutamide arm were event-free at 12 months (84% vs 64%).
A pre-specified subgroup analysis showed that rPFS was prolonged for patients on the enzalutamide arm for all subgroups, regardless of age, geographic region, Gleason score, volume of disease, or receipt of prior docetaxel therapy.
Patients on the enzalutamide arm also had an 81% improvement in the risk of prostate-specific antigen (PSA) progression compared with those on the placebo arm (HR, 0.19; 95% CI, 0.13–0.26; P < .0001). At 12 months, 91% of the enzalutamide arm had not experienced PSA progression compared with 63% of the placebo arm.
A significantly higher portion of the enzalutamide arm achieved an undetectable PSA rate compared with the placebo arm (68.1% vs 17.6%; P < .0001). The objective response rate was also significantly higher for the enzalutamide arm (83.1% vs 63.7%; P < .0001), and more patients in this arm achieved a complete response (36.7% vs 23.1%) and a partial response (46.3% vs 40.7%).
“This definitely changes practice,” David Friedland, MD, medical oncologist at UPMC Hillman Cancer Center, said during an interview with Cancer Network about the trial results. “We’ve been using other agents besides enzalutamide in this setting, but this gives us another option.” He noted that the ARCHES trial shows that enzalutamide can benefit patients with low or high volume disease. “A lot of the other studies showed only a benefit in patients with high volume disease,” he said.
As for safety, the incidence of adverse events in the enzalutamide arm was similar to the placebo arm (85.1% vs 85.9%). The incidence of grade 3 or higher adverse events were also similar (24.3% vs 25.6%). Compared with the toxicity of similar agents, like abiraterone and docetaxel, enzalutamide is easier to give to patients, Friedland said.
“The only unique side effect with [enzalutamide] is the small risk of seizures,” he said. Two patients on each arm reported a seizure. “For me it’s not a consideration in deciding whether or not to use it, unless maybe I had a patient with poorly controlled seizure disorder,” he said.
“It’s becoming a crowded field,” Friedland added. “There are several of these agents in trials and data is being reported. It seems like every day we’re hearing new results.”