Clinical Summary:

• Design/Population: The phase 3 PROTEUS trial evaulated apalutamide plus ADT in patients with newly diagnosed high-risk localized or locally advanced prostate cancer who underwent radical prostatectomy with pelvic lymph node dissection.
• Key Outcomes: Apalutamide plus ADT significantly improved response and survival outcomes compared to placebo. 
• Clinical Relevance: Perioperative apalutamide plus ADT may increase the curative potential of radical prostatectomy in high-risk localized or locally advanced prostate cancer, supporting this combined systemic and surgical approach as a potential new standard of care.

Transcript:

Mary-Ellen Taplin, MD, discusses the final analysis of the phase 3 PROTEUS trial, which demonstrated that perioperative apalutamide plus ADT improved pathologic responses and metastasis-free survival in patients with high-risk localized or locally advanced prostate cancer undergoing radical prostatectomy.

Dr Taplin presented these results in a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

Hello, my name is Mary-Ellen Taplin. I'm a medical oncologist at the Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School. 

Today we're going to talk about the PROTEUS trial. This is a phase 3 trial for men with localized high-risk prostate cancer. 

So, when we see a new patient with prostate cancer, they're assigned a risk category, low intermediate, or high risk. And the high-risk patients are generally offered prostatectomy or hormones and radiation as their primary treatment. However, with high-risk prostate cancer, we know the relapse rate is high. In some cases, that relapse rate can approach 70%. 

So, in cancers other than prostate cancer, there's often a combination of systemic therapy and surgery that's called neoadjuvant or adjuvant systemic therapy combined with surgery. However, in prostate cancer, these combinations have not been yet proven beneficial. So, PROTEUS sought to investigate whether 6 months of apalutamide combined with ADT before prostatectomy and 6 months after prostatectomy would improve patient outcomes. 

The control arm in this trial was placebo and androgen deprivation therapy. And the reason the control arm was androgen deprivation therapy rather than surgery alone was it was important to keep the trial blinded in order to follow patients for the number of years that was going to be necessary—5 to 7 years—to obtain a metastasis-free endpoint. 

So, the data for PROTEUS can be categorized as to 2 co-primary endpoints, several secondary endpoints, and several very important exploratory endpoints. So. let me start with the two co-primary endpoints. 

The first endpoint was what's called pathologic complete response, or minimal residual disease, which means less than 5 millimeters of tumor left in the prostate at the time of prostatectomy. So what we saw with this endpoint was that there was a ninefold improvement for apalutamide ADT in this major pathologic response compared to placebo and ADT. And an exploratory endpoint that's called residual cancer burden, which measures the residual cancer by its cellularity as well as size was also very positive. There was a 30% major pathologic response seen in the apalutamide cohort versus an 11% in the placebo cohort. So that's the first primary endpoint. 

The second primary endpoint is the metastasis-free survival, which measures any metastasis by PSMA PET scan or conventional imaging or death. And this endpoint showed a 20% reduction for apalutamide and ADT compared to placebo and ADT. So that's the 2 co-primary endpoints, both statistically significant, and an exploratory endpoint called investigator assessed MSS was even more positive for apalutamide ADT with a hazard ratio of 0.74, which represents a 26% reduction. 

So, these primary endpoints, both positive and also supported by several positive secondary endpoints, including event-free survival—that’s recurrence by any means—and a really exciting secondary endpoint that was positive was the time to subsequent therapy, which showed a 33% reduction and almost a 3-year difference for the apalutamide ADT cohort compared to the placebo ADT cohort. And in fact, there was a 29% reduction in receiving any subsequent androgen deprivation therapy or radiation to the pelvis. So, we know that these secondary treatments can cause significant morbidity and reduction in quality of life. 

So, these PROTEUS endpoints, the 2 primary endpoints, the secondary endpoints, exploratory endpoints, all support this type of treatment, 6 months of ADT and apalutamide prior to and after prostatectomy, as a potential new standard of care for patients with localized high-risk prostate cancer. 

Source:

Taplin ME, Gleave M, Shore ND, et al. Perioperative (neoadjuvant and adjuvant) apalutamide (APA) + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT with radical prostatectomy (RP) in high-risk localized or locally advanced prostate cancer (HR LPC/LAPC): Final analysis of the PROTEUS phase 3 study. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA1.