PROTEUS: apalutamide plus ADT demonstrates significant improvements in pCR and metastasis-free survival in high-risk prostate cancer
Patients with high-risk localized or locally advanced prostate cancer (HR LPC/LAPC) face higher rates of relapse than patients with low-risk disease despite curative-intent treatment, with up to 50% of HR LPC/LAPC patients relapsing within five years after radical prostatectomy. There is a need for treatments which increase curative success and prolong relapse for patients with high-risk disease. 1,2
The Phase III PROTEUS trial (NCT03767244), presented at the 2026 American Society of Clinical Oncology (ASCO) Meeting, examined whether neoadjuvant and adjuvant apalutamide would improve curative success for patients with HR LPC/LAPC. 2,109 patients with newly diagnosed HR LPC/LAPC were randomized 1:1 to receive neoadjuvant and adjuvant apalutamide plus androgen deprivation therapy (ADT) or placebo plus ADT with radical prostatectomy. The dual primary endpoints were pathological complete response (pCR) or minimal residual disease (MRD) with metastasis-free survival (MFS). Secondary endpoints included event-free survival (EFS), time to first subsequent treatment, time to distant metastasis and safety. 3
Both primary endpoints were met, with a significantly higher rate of pCR/MRD of 8.9% with apalutamide and ADT, compared with 1.0% for placebo and ADT (OR 10.17, 95% CI: 5.27-19.64). MFS by blinded independent central review was also significantly higher with apalutamide than placebo (HR 0.8, 95% CI: 0.67-0.96) and at five-year follow-up, the probability of MFS was 78.2% for the apalutamide group and 73.5% in the placebo group. All secondary endpoints showed an improvement with apalutamide over placebo. There was a higher rate of grade 3 or 4 treatment-emergent adverse events (TEAEs) with apalutamide in comparison to placebo (39.6% vs 31.0% respectively) and discontinuation due to TEAEs was also higher with apalutamide (7.4% vs 2.7% with placebo). 3
Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute, Boston, MA, comments on the results and how this could shape treatment of prostate cancer:
“We’re very thrilled with those endpoints, and they support this type of treatment, apalutamide and androgen deprivation therapy, six months before prostatectomy, six months after as a new standard treatment option for men with localized high-risk prostate cancer.”
The results from the PROTEUS trial indicate that apalutamide + ADT improves the curative success of radical prostatectomy and increases disease control compared with placebo + ADT. This supports the adoption of perioperative apalutamide with ADT as a new standard of care treatment for HR LPC/LAPC, neoadjuvant and adjuvant to radical prostatectomy.
References:
1. Chen W-H, Lee YK, Kuo H-C, Wang J-H, Jiang Y-H. Oncological and functional outcomes of high-risk and very high-risk prostate cancer patients after robot-assisted radical prostatectomy. PLoS One. 2023;18(3). https://doi.org/10.1371/journal.pone.0282494.
2. Eiber M, Aebersold DM, Valcarcel diaz A, Wetterauer C, Bach M, Camarrone F, et al. PHAROS, a real-world multi-country European study on patients with high-risk localised and locally advanced prostate cancer receiving radical treatment. J Clin Oncol. 2024;42(Suppl 16):Abstr 5027.
3. Taplin M-E, Gleave M, Shore ND, Lopez-Gitlitz A, Fretschmer A, Efstathiou E, 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. J Clin Oncol. 2026;44(suppl 17):Abstr LBA1.
