CHICAGO — The PROTEUS phase 3 clinical trial demonstrated that adding apalutamide to androgen-deprivation therapy (ADT) before and after surgery improved outcomes for patients with high-risk localized or locally advanced prostate cancer. Results showed a 20 percent reduced risk of metastasis or death and an increase in pathologic response compared to ADT alone.
The randomized, double-blind, placebo-controlled trial enrolled 2,109 patients with newly diagnosed high-risk prostate cancer. Participants received either apalutamide plus ADT or placebo plus ADT for six months before and after radical prostatectomy with pelvic lymph-node dissection. The two primary endpoints were pathologic response and metastasis-free survival, assessed using conventional imaging and PSMA-PET imaging.
After a median follow-up of 61.7 months, the five-year metastasis-free survival probability was 78.2 percent in the apalutamide plus ADT group, compared to 73.5 percent in the ADT-alone group. Patients treated with apalutamide plus ADT were nine times more likely to have little to no cancer present at surgery. Specifically, 8.9 percent in the apalutamide group achieved a pathologic complete response or minimal residual disease, versus 1.0 percent in the control group. The trial also delayed the need for subsequent therapy by 33 months.
"We have a paradigm-changing phase 3 clinical trial," said Mary-Ellen Taplin, MD, a medical oncologist at Dana-Farber Cancer Institute and principal investigator of the PROTEUS trial. "This type of treatment regimen that combines systemic therapy with surgery is standard in other aggressive cancers and now has proven benefit for patients with high-risk localized or locally advanced prostate cancer."
Taplin presented the findings in a plenary session at the American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago. The results were simultaneously published in the New England Journal of Medicine.
Adam Kibel, MD, chair of the Department of Urology at Mass General Brigham and a principal investigator of the trial, called the outcomes promising. "As a urologic surgeon who cares for patients with advanced prostate cancer, I am thrilled by the improvements in pathology and metastasis-free survival we observed in the PROTEUS trial," Kibel said. "The outcomes of this trial have the potential to reshape the standard of care for our patients with high-risk prostate cancer."
Side effects in the trial were consistent with previously reported data on apalutamide. Apalutamide is already approved for metastatic castration-sensitive and nonmetastatic castration-resistant prostate cancer. Current standard treatment for high-risk prostate cancer includes surgery and/or radiotherapy with ADT, but up to 50 percent of patients relapse within five years. More than 330,000 people are diagnosed with prostate cancer annually in the U.S., with up to 20 percent facing the aggressive, high-risk form.