Results from the phase 3 PROTEUS study found that for people with localised high-risk prostate cancer, treatment with apalutamide and androgen deprivation therapy (ADT) along with surgery could delay or prevent worsening of the disease, with few additional side-effects, better than ADT and surgery. The research was presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
The trial was designed to evaluate whether administering apalutamide and ADT before and after surgery reduces the development of metastases compared to placebo and ADT. The study included 2,109 participants across 118 hospitals globally. The median age of participants was 66, and 69.4 per cent were White, 19.3 per cent were Asian, and 3.7 per cent were Black or African American. Participants were treatment-naïve, and had a median prostate-specific antigen value of 14.8ng/ml, and a majority had a Gleason score of 8 or higher, indicating high-risk disease.
Participants were divided into two groups. All participants had a radical prostatectomy and received ADT for six months before and six months after surgery, while one group (1,057) received apalutamide, with the other (1,052) receiving a placebo.
After a median follow-up of about 62 months, results showed that giving apalutamide before and after radical prostatectomy improved treatment outcomes for people with high-risk prostate cancer.
People who got neoadjuvant apalutamide were about 10 times more likely to have a major reduction of tumour cells by the time they got prostate surgery: 8.9 per cent of people in the apalutamide group and 1 per cent in the placebo group achieved pathologic complete response or minimal residual disease.
Participants who got apalutamide had a 29 per cent lower risk that the prostate cancer would recur. Neoadjuvant and adjuvant apalutamide treatment prolonged the median event-free survival from 38.4 months in the placebo group to 57.1 months in the apalutamide group.
Apalutamide treatment lowered the risk of metastasis by 20 per cent compared to a placebo, and it improved five-year metastasis-free survival from 73.5 per cent in the placebo group to 78.2 per cent in the apalutamide group.
Compared to the placebo group, the apalutamide group was more likely to have severe and life-threatening (grades 3 to 4) adverse events, which occurred in 39.6 per cent and 31 per cent of participants, respectively. The most common adverse events in both groups were a build-up of lymphatic fluid (lymphocele) and urinary tract infection. Pulmonary embolism also occurred in the placebo group. Rashes were the most common reason people discontinued treatment in the apalutamide group.
“This is the first convincing randomised control trial demonstrating improvement in clinically meaningful endpoints in patients with high-risk localised prostate cancer treated with radical prostatectomy. With pathologic complete response rates near 9 per cent and metastasis-free survival improvements of 20 per cent compared with ADT alone, the addition of apalutamide to ADT clearly improves outcomes in surgical patients at high risk for relapse. That said, we haven’t yet compared it directly to current options like upfront surgery or the combination of radiation and androgen deprivation therapy,” said Dr William K Oh, Yale School of Medicine and an ASCO expert in genitourinary cancers.
Researchers will now use PROTEUS data to evaluate the association between the extent of tumour shrinkage and long-term outcomes. Further analyses will investigate biomarkers to help predict which patients will benefit from apalutamide and if the treatment may eventually stop working.
In addition, researchers will analyse patient-reported outcomes to understand the effects of treatment on quality-of-life.
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