SAN FRANCISCO -- Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) delayed time to progression in patients with metastatic hormone-sensitive prostate cancer, the phase III ARCHES trial showed.
In the study of over 1,000 patients, radiographic progression-free survival (rPFS) was not reached in the combination arm compared with 19.4 months in the ADT alone arm (HR 0.39, 95% CI 0.30-0.50, P<0.0001), reported Andrew Armstrong, MD, of Duke Cancer Institute in Durham, North Carolina.
Secondary endpoints also favored the enzalutamide arm: prostate-specific antigen (PSA) progression was improved (HR 0.19, 95% CI 0.13-0.26, P<0.0001) as were rates of undetectable PSA (68.1% vs 17.6% with ADT, P<0.0001), as presented here at the Genitourinary Cancers Symposium.
Armstrong pointed to the subset of patients with prior docetaxel exposure, where enzalutamide-ADT still showed rPFS benefit over ADT plus placebo (HR 0.53, 95% CI 0.31-0.92).
"Sequential use of therapy may be the most efficacious, particularly for high-volume disease," Armstrong told MedPage Today.
"Docetaxel followed by enzalutamide is where I felt this was most practice-changing for next week," he said. "Instead of an either-or decision, it's going to be a both decision."
Enzalutamide is a nonsteroidal antiandrogen that was first approved in 2012 for metastatic castration-resistant disease.
"The study has clearly met its primary endpoint of rPFS, which is very useful, but we don't actually know for sure that that correlates with overall survival yet in this setting," cautioned Ian Davis, MD, of Monash University in Melbourne, Australia. "I suspect it probably will, but the study is still fairly immature."
At the time of the analysis, which had a median follow-up of 14.4 months, no significant difference in overall survival (OS) was seen between the two arms.
"We find ourselves in an interesting situation at the moment in the setting of M1 hormone-sensitive prostate cancer," said Davis, who explained that both docetaxel and abiraterone (Zytiga) have already shown substantial improvements in OS when added to ADT in this setting.
"I think it'd be premature to say that enzalutamide is occupying the same space," he said, pointing to the lack of OS data.
But here he declared a conflict of interest. Davis is global chair of ENZAMET, a similar study to ARCHES but with two key differences. In ENZAMET, patients received enzalutamide plus docetaxel-ADT in the investigational arm or docetaxel-ADT alone in the control group, and the primary endpoint is OS, with an interim analysis expected soon.
In ARCHES, as noted by Armstrong, 18% of patients had received docetaxel with ADT, but these patients had to have completed the chemotherapy before randomization.
"We hope that both of those studies will provide complementary information to support the use of enzalutamide in this setting," said Davis.
"I would anticipate by the end of the year we're going to have many options for men with metastatic hormone-sensitive disease," Armstrong said, pointing to abiraterone, docetaxel, enzalutamide, and possibly apalutamide (Erleada) as well. "And just like in the castration-resistant setting, some of these choices are going to be dictated by patient-specific factors, payer factors, costs, toxicities, rather than efficacy, because many of these drugs are very efficacious and equally efficacious."
The ARCHES trial was a placebo-controlled trial that included 1,150 patients with metastatic hormone-sensitive prostate cancer. Median patient age was 70 years old with an ECOG performance status of 0 or 1.
The combination also improved rates of objective response over ADT alone (83.1% vs 63.7%, respectively, P<0.0001) and reduced the risk of starting a new antineoplastic therapy (HR 0.28, 95% CI 0.20-0.40, P<0.0001). No difference between the two groups with regard to deterioration of urinary symptoms (HR 0.88, 95% CI 0.72-1.08) was seen.
Any grade adverse events (AEs) were similar between the enzalutamide group and the ADT alone group (85.1% vs 85.9%, respectively), as were grade 3/4 AEs (24.3% vs 25.6%).
Armstrong disclosed relationships with Astellas, AstraZeneca, Bayer, Clovis Oncology, Dendreon, Janssen, Medivation, Pfizer, Sanofi, and others.
Davis reported relationships with Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Novartis, Pfizer, Roche, and Sanofi.
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