J&J: apalutamide cuts recurrence risk 62% in localised prostate cancer

Johnson & Johnson has reported new Phase 3 substudy data showing that perioperative use of apalutamide (Erleada) combined with androgen deprivation therapy (ADT) reduces the risk of disease recurrence or death by 62% compared with radical prostatectomy alone in patients with high-risk localised or locally advanced prostate cancer.

The results were presented as a late-breaking abstract at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid and accepted for publication in European Urology. They build on the primary PROTEUS study findings, which were presented at the ASCO Annual Meeting in May 2026 and published in the New England Journal of Medicine.

Trial results

The PROTEUS substudy enrolled 408 patients with newly diagnosed, non-metastatic, high-risk disease who were candidates for surgery. Participants received apalutamide at 240 mg orally once daily, plus ADT, for six 28-day cycles before and six cycles after radical prostatectomy with pelvic lymph node dissection. The control arm underwent surgery followed by standard institutional practice or observation.

At a median follow-up of 37.8 months, the treatment regimen produced a hazard ratio of 0.38 (95% CI, 0.26–0.55; p<0.0001) for event-free survival, the primary endpoint. Median EFS was not reached in the apalutamide arm, against 19.1 months for surgery alone. At three years, 63% of treated patients remained event-free versus 41.4% in the control group.

Secondary and exploratory endpoints supported the primary finding. Metastasis-free survival showed a 51% lower risk of distant metastasis or death (HR, 0.49; nominal p=0.0193), while time to first subsequent therapy showed a 71% lower risk of needing further treatment (HR, 0.29; nominal p<0.0001). At three years, 64.6% of apalutamide-treated patients remained free from subsequent therapy, against 32% in the surgery-alone arm.

Grade 3 or 4 treatment-emergent adverse events were reported in 31% of patients on apalutamide plus ADT, compared with 22% on surgery alone. The most common events with apalutamide were hot flush (64%) and urinary incontinence (63%). No treatment-related deaths were recorded in either arm. J&J noted that apalutamide has not been approved for this indication and that overall survival follow-up is ongoing.

Alberto Briganti, Professor of Urology at IRCCS San Raffaele Hospital in Milan, said the substudy's findings suggest it may be possible "to build on surgery and help more patients achieve lasting disease control" by adding apalutamide plus ADT to the perioperative regimen.

Market and regulatory context

Prostate cancer is the most commonly diagnosed cancer among European men, with approximately 462,000 new cases recorded across Europe in 2024. An estimated 15% of patients present with high-risk disease, and biochemical recurrence rates following radical prostatectomy can exceed 50% at five years, giving the perioperative setting clear clinical and commercial relevance.

Apalutamide already holds European Commission approval in two other prostate cancer indications: non-metastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer. Regulatory submission for the high-risk localised setting would depend on mature overall survival data, which are not yet available. A separate Phase 3 study, ATLAS, is evaluating apalutamide in combination with radiotherapy in locally advanced disease, indicating J&J is pursuing multiple entry points in earlier-line prostate cancer.

The perioperative intensification approach places apalutamide in direct competition with other androgen receptor pathway inhibitors and with neoadjuvant chemohormonal regimens under investigation. The release of full PROTEUS survival data will be a critical catalyst for any regulatory discussion with the EMA.