An international phase 3 clinical trial led by principal investigator Mary Ellen Taplin, MD, a clinical oncologist at Dana-Farber Cancer Institute, met both primary endpoints when treating high-risk localized and locally advanced prostate cancer patients with apalutamide, a next-generation neoadjuvant androgen receptor pathway inhibitor (ARPI), and hormone therapy before and after prostate cancer surgery, resulting in more significant pathological responses and lower risk of metastasis or death. Dr. Adam Kivell, chief of urology at Brigham Mass General;
These potentially practice-changing findings will be presented by Taplin today in the plenary session of the American Society of Clinical Oncology (ASCO) annual meeting in Chicago and will be published in the New England Journal of Medicine.
More than 330,000 people are diagnosed with prostate cancer each year, and up to 20% have aggressive prostate cancer and are considered at high risk of recurrence after first-line treatment. Current standard treatment includes radical prostatectomy and/or radiation therapy with androgen-depleting hormone therapy (ADT). Although this treatment is effective for some people, up to 50% of patients experience recurrence within 5 years. This highlights the need for improved regimens that act earlier and more intensively to improve outcomes.
Reducing the risk of prostate cancer recurrence and death through improved initial treatment planning has long been an unmet need for men with localized high-risk prostate cancer. The PROTEUS study aims to help men whose cancer is still considered curable but is more likely to come back or spread. ”
Mary Ellen Taplin, MD, medical oncologist, Dana-Farber Cancer Institute
PROTEUS is a randomized, double-blind, placebo-controlled, Phase 3 trial in 2,109 patients with newly diagnosed, high-risk, localized or locally advanced prostate cancer designed to evaluate the addition of apalutamide therapy before and after surgery. Apalutamide is approved for use in metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer. A previous Dana-Farber study led by Taplin also found that intensive ADT before surgery showed promise in patients with high-risk localized prostate cancer. These findings supported the exploration of apalutamide in the perioperative or perioperative setting in this patient population.
Participating patients received oral apalutamide and ADT or placebo and ADT for 6 months before and after radical prostatectomy with pelvic lymph node dissection. The study’s two primary endpoints included measuring participants’ pathological response and metastasis-free survival using both traditional imaging (bone scan and cat scan) and PSMA-PET imaging, a new approach to measuring disease status. After a median follow-up of 61.7 months, the combination of apalutamide and ADT reduced the risk of metastasis or death by 20 percent, and the 5-year probability of metastasis-free survival was 78.2 percent, compared with 73.5 percent with hormone therapy alone. Patients who received the combination of apalutamide and hormone therapy were nine times more likely to have little or no cancer at the time of surgery, and 8.9% experienced a complete pathologic response or minimal residual disease, compared with 1.0% of patients who received hormone therapy alone. Remarkably, this study helped delay subsequent treatment by 33 months.
“As a urologic surgeon who treats patients with advanced prostate cancer, I am excited by the significant improvements in pathology and metastasis-free survival observed in the PROTEUS trial,” said Kibel, senior author of the ASCO publication and New England Journal of Medicine manuscript. “The results of this trial have the potential to reshape the standard of care for patients with high-risk prostate cancer.”
Side effects were consistent with data from previously reported studies.
“We are conducting a paradigm-changing phase 3 clinical trial,” Taplin said. “This type of treatment plan, combining systemic therapy and surgery, is standard for other aggressive cancers and is now proven to be beneficial for patients with high-risk locally or locally advanced prostate cancer.”
sauce:
Dana-Farber Cancer Institute
Reference magazines:
Taplin, M.-E. others. (2026). Perioperative apalutamide in high-risk localized prostate cancer. New England Medical Journal. DOI: 10.1056/NEJMoa2603878. https://www.nejm.org/doi/10.1056/NEJMoa2603878
