Enzalutamide plus ADT improves outcomes in metastatic hormone-sensitive prostate cancer
Enzalutamide in combination with androgen deprivation therapy (ADT) is shown to improve outcomes vs ADT alone in men with metastatic hormone-sensitive prostate cancer in the phase III ARCHES trial.
Among 1,150 patients randomized 1:1 to receive enzalutamide (160 mg/day) plus ADT or placebo plus ADT, the primary endpoint of radiographic progression-free survival (rPFS) was significantly improved in the enzalutamide vs placebo group after a median follow-up of 14.4 months (median rPFS, not reached vs 19.4 months; hazard ratio [HR], 0.39; 95 percent confidence interval [CI], 0.30 to 0.50; p<0.0001). [Armstrong AJ, et al, ASCO GU 2019, abstract 687]
“Similar significant improvements in rPFS were found with enzalutamide plus ADT in prespecified subgroups of disease volume, pattern of disease localization at baseline, geographic region, and prior use of docetaxel [HRs, 0.24–0.53],” reported lead investigator Professor Andrew Armstrong of the Duke Cancer Institute, Durham, North Carolina, US.
Patients treated with enzalutamide plus ADT also showed significant improvements in time to prostate-specific antigen (PSA) progression (HR, 0.19; 95 percent CI, 0.13 to 0.26; p<0.0001) and time to initiation of new antineoplastic therapy (HR, 0.28; 95 percent CI, 0.20 to 0.40; p<0.0001) compared with those treated with ADT alone.
“Median time to castration resistance was not reached in the enzalutamide group compared with 13.9 months in the placebo group [HR, 0.28; p<0.0001],” said Armstrong.
In addition, significantly more patients achieved undetectable PSA levels (<0.2 ng/mL) with enzalutamide plus ADT vs ADT alone (68.1 percent vs 17.6 percent; p<0.0001). Objective response rate was also significantly higher with enzalutamide plus ADT, at 83.1 percent, compared with 63.7 percent with ADT alone (p<0.0001).
“Overall survival [OS] data are immature. At the time of data cut-off, there were 84 deaths, with the HR favouring enzalutamide plus ADT,” noted Armstrong. “Final OS analysis will be conducted after 342 deaths.”
In terms of safety, grade 3/4 adverse events (AEs) were reported in 23.6 percent of patients treated with enzalutamide plus ADT vs 24.7 percent of patients treated with ADT alone, with no unexpected AEs. “The most common AEs in the enzalutamide group included hot flushes, fatigue, arthralgia, hypertension, nausea, musculoskeletal pain, diarrhoea, asthenia, and dizziness,” said Armstrong.
“Enzalutamide has previously shown benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer. Its efficacy in combination with ADT had remained unclear until these results from the ARCHES trial became available,” he explained.At baseline, 67 percent of the ARCHES patients had distant metastasis, 63 percent had high-volume disease, and 18 percent had received prior docetaxel therapy.